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!The amino acid sequence of MCD peptide <ref>{{cite journal |last1=Argiolas |first1=A |last2=Herring |first2=P |last3= Pisano |first3=JJ |year=1985 |title= Amino Acid Sequence of Bumblebee MCD Peptide: A New Mast Cell Degranulating Peptide From the Venom of the Bumblebee Megabombus pennsylvanicus |journal= Peptides |volume= 6 | issue=3 |pages= 431–436 |url= |doi= }}</ref>
!The amino acid sequence of MCD peptide <ref>{{cite journal |last1=Argiolas |first1=A |last2=Herring |first2=P |last3= Pisano |first3=JJ |year=1985 |title= Amino Acid Sequence of Bumblebee MCD Peptide: A New Mast Cell Degranulating Peptide From the Venom of the Bumblebee Megabombus pennsylvanicus |journal= Peptides |volume= 6 | issue=3 |pages= 431–436 |url= |doi=10.1016/0196-9781(85)90410-3 }}</ref>
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| bgcolor="#eeeeee" |Met - Cys - Ile - Cys - Lys - Asn - Gly - Lys - Pro - Leu - Pro - Gly - Phe - Ile - Gly - Lys - Ile - Cys - Arg - Lys - Ile - Cys - Met - Met - Gln - Gln -Thr - His(NH2)
| bgcolor="#eeeeee" |Met - Cys - Ile - Cys - Lys - Asn - Gly - Lys - Pro - Leu - Pro - Gly - Phe - Ile - Gly - Lys - Ile - Cys - Arg - Lys - Ile - Cys - Met - Met - Gln - Gln -Thr - His(NH2)
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== Source ==
== Source ==
MCD peptide is a component of [[bumblebee]] (''Megabombus pennsylvanicus'') [[venom]] <ref>{{cite journal |last1=Breithaupt |first1= H |last2= Habermann |first2= E |year= 1968 |title= Mastzelldegranulierendes Peptid (MCD-Peptid) aus Bienengift: Isolierung, biochemische und pharmakologische Eigenschaften |journal= Naunyn-Schmiedebergs Arch. Pharmak. exp. Path. |volume= 261 |issue= |pages= 252–270 |url= |doi= }}</ref>. In addition to MCD peptide, [[melittin]] and [[apamin]] have also been identified in this venom and are also described as voltage-dependent channel blockers. MCD peptide is also present in the venom of the [[honey bee]] ''[[Apis mellifera]]'' <ref>{{cite journal |last1=Bessone |first1=R |last2= Martin-Eauclaire |first2= MF |last3= Crest |first3= M |last4= Mourre |first4= C |year= 2004 |title= Heterogeneous competition of Kv1 channel toxins with kaliotoxin for binding in rat brain: autoradiographic analysis |journal= Neurochem Int. |volume= 45 |issue= 7 |pages= 1039–47 |url= |doi= }}</ref>.
MCD peptide is a component of [[bumblebee]] (''Megabombus pennsylvanicus'') [[venom]] <ref>{{cite journal |last1=Breithaupt |first1= H |last2= Habermann |first2= E |year= 1968 |title= Mastzelldegranulierendes Peptid (MCD-Peptid) aus Bienengift: Isolierung, biochemische und pharmakologische Eigenschaften |journal= Naunyn-Schmiedebergs Arch. Pharmak. Exp. Path. |volume= 261 |issue= |pages= 252–270 |url= |doi=10.1007/BF00536989 }}</ref>. In addition to MCD peptide, [[melittin]] and [[apamin]] have also been identified in this venom and are also described as voltage-dependent channel blockers. MCD peptide is also present in the venom of the [[honey bee]] ''[[Apis mellifera]]'' <ref>{{cite journal |last1=Bessone |first1=R |last2= Martin-Eauclaire |first2= MF |last3= Crest |first3= M |last4= Mourre |first4= C |year= 2004 |title= Heterogeneous competition of Kv1 channel toxins with kaliotoxin for binding in rat brain: autoradiographic analysis |journal= Neurochem Int. |volume= 45 |pmid=15337303 |issue= 7 |pages= 1039–47 |url= |doi=10.1016/j.neuint.2004.05.006 }}</ref>.


== Chemistry ==
== Chemistry ==
MCD peptide is a cationic 22-amino acid residue peptide with two disulfide bridges <ref>{{cite journal |last1= Buku |first1= A |year= 1999 |title= Mast cell degranulating (MCD) peptide: a prototypic peptide in allergy and inflammation |journal= Peptides |volume= 20 |issue= 3 |pages= 415–20 |url= |doi= }}</ref>. Although the MCD peptide sequence shows similarity with apamin <ref>{{cite journal |last1=Gmachl |first1= M |last2= Kreil |first2= G |year= 1995 |title= The precursors of the bee Venom Constituents Apamin and MCD Peptide Are Encoded by two Genes in Tandem Which Share the Same 3’- Exon |journal= J Biol Chem |volume= 270 |issue= |pages= 12704–12708 |url= |doi= }}</ref>, they have different toxic properties. MCD peptide belongs to a large family composed of numerous derivatives detecting specific targets and displaying different toxic effects <ref>{{cite journal |last1= Buku |first1= A |year= 1999 |title= Mast cell degranulating (MCD) peptide: a prototypic peptide in allergy and inflammation |journal= Peptides |volume= 20 |issue= 3 |pages= 415–20 |url= |doi= }}</ref>.
MCD peptide is a cationic 22-amino acid residue peptide with two disulfide bridges <ref>{{cite journal |last1= Buku |first1= A |year= 1999 |title= Mast cell degranulating (MCD) peptide: a prototypic peptide in allergy and inflammation |journal= Peptides |volume= 20 |pmid= 10447103 |issue= 3 |pages= 415–20 |url= |doi=10.1016/S0196-9781(98)00167-3 }}</ref>. Although the MCD peptide sequence shows similarity with apamin <ref>{{cite journal |last1=Gmachl |first1= M |last2= Kreil |first2= G |year= 1995 |title= The precursors of the bee Venom Constituents Apamin and MCD Peptide Are Encoded by two Genes in Tandem Which Share the Same 3’- Exon |journal= J Biol Chem |volume= 270 |pmid=7759523 |issue= 21|pages= 12704–12708 |url= |doi=10.1074/jbc.270.21.12704 }}</ref>, they have different toxic properties. MCD peptide belongs to a large family composed of numerous derivatives detecting specific targets and displaying different toxic effects <ref>{{cite journal |last1= Buku |first1= A |year= 1999 |title= Mast cell degranulating (MCD) peptide: a prototypic peptide in allergy and inflammation |journal= Peptides |volume= 20 |pmid= 10447103 |issue= 3 |pages= 415–20 |url= |doi=10.1016/S0196-9781(98)00167-3 }}</ref>.


== Targets ==
== Targets ==
MCD peptide has [[immunotoxic]] as well as [[neurotoxic]] properties due to different active sites of the MCD peptide <ref>{{cite journal |last1=Dreyer |first1= F |year= 1990 |title= Peptide Toxins and potassium channels |journal= Rev. Physiol. Biochem. Pharmacol |volume= 115 |issue= |pages= |url= |doi= }}</ref>. The MCD peptide has an immunotoxic effect on [[mast cells]] <ref>{{cite journal |last1=Argiolas |first1=A |last2=Herring |first2=P |last3= Pisano |first3=JJ |year=1985 |title= Amino Acid Sequence of Bumblebee MCD Peptide: A New Mast Cell Degranulating Peptide From the Venom of the Bumblebee Megabombus pennsylvanicus |journal= Peptides |volume= 6 | issue=3 |pages= 431–436 |url= |doi= }}</ref> by releasing histamine from these cells <ref>{{cite journal |last1=King |first1= TP |last2= Jim |first2= SY |last3= Wittkowski |first3= KM |year= 2003 |title= Inflammatory role of two venom components of yellow jackets (Vespula vulgaris): a mast cell degranulating peptide mastoparan and phospholipase A1 |journal= Int. Arch. Allergy Immunol |volume= 131 |issue= 1 |pages= 25–32 |url= |doi= }}</ref>. MCD peptide has also been described as a potent modulator of voltage-gated ionic channels. It binds to several subclasses of voltage-gated potassium channels (Kv channels), including [[Kv1.1]], [[Kv1.6]], and less potently to [[Kv1.2]] <ref>{{cite journal |last1= Pongs |first1= O | year=1992 |title= Molecular biology of voltage-dependent potassium channels |journal= Physiol. Rev |volume=72 |issue= | pages=69–88.|url=|doi=}}</ref> <ref>{{cite journal |last1=Grissmer |first1= S |last2= Nguyen |first2= AN |last3= Aiyar |first3= J |last4= Hanson |first4= DC |last5= Mather |first5= RJ |last6= Gurman |first6= GA |last7= Karmilowicz |first7= MJ |last8= Auperin |first8= DD |last9= Chandy |first9= KG |year= 1994 |title= Pharmacological characterization of five cloned voltage-gated K+ channels, types Kv1.1, 1.2, 1.3, 1.5, and 3.1, stably expressed in mammalian cell lines |journal= Mol Pharmacol |volume= 45 |issue= |pages= 1227–1234 |url= |doi= }}</ref> <ref>{{cite journal |last1=Harvey |first1= AL |year= 1997 |title= Recent studies on dendrotoxins and potassium ion channels |journal= Gen. Pharmacol |volume= 28 |issue= |pages= 7–12 |url= |doi= }}</ref> <ref>{{cite journal |last1= Stühmer |first1=M |last2= Ruppersberg |first2=J |last3= Schröter |first3=K | last4= Sakmann |first4=B | last5= Stocker |first5=M| last6= Giese |first6=K| last7= Perschke |first7=A | last8= Baumann |first8=A | last9= Pongs |first9=O | year=1989 |title= Molecular basis of functional diversity of voltage-gated potassium channels in mammalian brain |journal= EMBO J |volume=8 |issue=| pages=3235–3244|url= |doi=}}</ref>. Accordingly, MCD peptide can act in various regions of rat brain, including cerebellum, brainstem, hypothalamus, striatum, midbrain, cortex <ref>{{cite journal |last1=Dreyer |first1= F |year= 1990 |title= Peptide Toxins and potassium channels |journal= Rev. Physiol. Biochem. Pharmacol |volume= 115 |issue= |pages= |url= |doi= }}</ref> <ref>{{cite journal |last1= Taylor |first1=J |last2= Bidard |first2=J |last3= Lazdunski |first3= M |year=1984|title= The characterization of high affinity binding sites in rat brain for the mast cell degranulating peptide from bee venom using purified monoiodinated peptide |journal= J Biol Chem |volume=259 |issue=2 |pages=13957–13967|url= |doi=}}</ref>, and hippocampus <ref>{{cite journal |last1=Dreyer |first1= F |year= 1990 |title= Peptide Toxins and potassium channels |journal= Rev. Physiol. Biochem. Pharmacol |volume= 115 |issue= |pages= |url= |doi= }}</ref>. However, MCD peptide shows no binding activity in the peripheral neuronal system <ref>{{cite journal |last1= Taylor |first1=J |last2= Bidard |first2=J |last3= Lazdunski |first3= M |year=1984|title= The characterization of high affinity binding sites in rat brain for the mast cell degranulating peptide from bee venom using purified monoiodinated peptide |journal= J Biol Chem |volume=259 |issue=2 |pages=13957–13967|url= |doi=}}</ref>.
MCD peptide has [[immunotoxic]] as well as [[neurotoxic]] properties due to different active sites of the MCD peptide <ref>{{cite journal |last1=Dreyer |first1= F |year= 1990 |title= Peptide Toxins and potassium channels |journal= Rev. Physiol. Biochem. Pharmacol |volume= 115 |issue= |pages= |url= |doi= }}</ref>. The MCD peptide has an immunotoxic effect on [[mast cells]] <ref>{{cite journal |last1=Argiolas |first1=A |last2=Herring |first2=P |last3= Pisano |first3=JJ |year=1985 |title= Amino Acid Sequence of Bumblebee MCD Peptide: A New Mast Cell Degranulating Peptide From the Venom of the Bumblebee Megabombus pennsylvanicus |journal= Peptides |volume= 6 | issue=3 |pages= 431–436 |url= |doi=10.1016/0196-9781(85)90410-3 }}</ref> by releasing histamine from these cells <ref>{{cite journal |last1=King |first1= TP |last2= Jim |first2= SY |last3= Wittkowski |first3= KM |year= 2003 |title= Inflammatory role of two venom components of yellow jackets (Vespula vulgaris): a mast cell degranulating peptide mastoparan and phospholipase A1 |journal= Int. Arch. Allergy Immunol |volume= 131 |pmid=12759486 |issue= 1 |pages= 25–32 |url= |doi=10.1159/000070431 }}</ref>. MCD peptide has also been described as a potent modulator of voltage-gated ionic channels. It binds to several subclasses of voltage-gated potassium channels (Kv channels), including [[Kv1.1]], [[Kv1.6]], and less potently to [[Kv1.2]] <ref>{{cite journal |last1= Pongs |first1= O | year=1992 |title= Molecular biology of voltage-dependent potassium channels |journal= Physiol. Rev |volume=72 |issue= | pages=69–88.|url=|doi=}}</ref> <ref>{{cite journal |last1=Grissmer |first1= S |last2= Nguyen |first2= AN |last3= Aiyar |first3= J |last4= Hanson |first4= DC |last5= Mather |first5= RJ |last6= Gurman |first6= GA |last7= Karmilowicz |first7= MJ |last8= Auperin |first8= DD |last9= Chandy |first9= KG |year= 1994 |title= Pharmacological characterization of five cloned voltage-gated K+ channels, types Kv1.1, 1.2, 1.3, 1.5, and 3.1, stably expressed in mammalian cell lines |journal= Mol Pharmacol |volume= 45 |pmid=7517498 |issue= 6|pages= 1227–1234 |url= |doi= }}</ref> <ref>{{cite journal |last1=Harvey |first1= AL |year= 1997 |title= Recent studies on dendrotoxins and potassium ion channels |journal= Gen. Pharmacol |volume= 28 |pmid=9112070 |issue= 1|pages= 7–12 |url= |doi= }}</ref> <ref>{{cite journal |last1= Stühmer |first1=M |last2= Ruppersberg |first2=J |last3= Schröter |first3=K | last4= Sakmann |first4=B | last5= Stocker |first5=M| last6= Giese |first6=K| last7= Perschke |first7=A | last8= Baumann |first8=A | last9= Pongs |first9=O | year=1989 |title= Molecular basis of functional diversity of voltage-gated potassium channels in mammalian brain |journal= EMBO J |volume=8 |pmid= 2555158 |issue=11| pages=3235–3244 |pmc= 401447|url= |doi=}}</ref>. Accordingly, MCD peptide can act in various regions of rat brain, including cerebellum, brainstem, hypothalamus, striatum, midbrain, cortex <ref>{{cite journal |last1=Dreyer |first1= F |year= 1990 |title= Peptide Toxins and potassium channels |journal= Rev. Physiol. Biochem. Pharmacol |volume= 115 |issue= |pages= |url= |doi= }}</ref> <ref>{{cite journal |last1= Taylor |first1=J |last2= Bidard |first2=J |last3= Lazdunski |first3= M |year=1984|title= The characterization of high affinity binding sites in rat brain for the mast cell degranulating peptide from bee venom using purified monoiodinated peptide |journal= J Biol Chem |volume=259 |issue=2 |pages=13957–13967|url= |doi=}}</ref>, and hippocampus <ref>{{cite journal |last1=Dreyer |first1= F |year= 1990 |title= Peptide Toxins and potassium channels |journal= Rev. Physiol. Biochem. Pharmacol |volume= 115 |issue= |pages= |url= |doi= }}</ref>. However, MCD peptide shows no binding activity in the peripheral neuronal system <ref>{{cite journal |last1= Taylor |first1=J |last2= Bidard |first2=J |last3= Lazdunski |first3= M |year=1984|title= The characterization of high affinity binding sites in rat brain for the mast cell degranulating peptide from bee venom using purified monoiodinated peptide |journal= J Biol Chem |volume=259 |issue=2 |pages=13957–13967|url= |doi=}}</ref>.


== Mode of action ==
== Mode of action ==
For its immunotoxic properties, a low concentration of MCD peptide can cause mast cell degranulation by releasing [[histamine]]; at higher concentrations it displays anti-inflammatory activities <ref>{{cite journal |last1=Dreyer |first1= F |year= 1990 |title= Peptide Toxins and potassium channels |journal= Rev. Physiol. Biochem. Pharmacol |volume= 115 |issue= |pages= |url= |doi= }}</ref>.
For its immunotoxic properties, a low concentration of MCD peptide can cause mast cell degranulation by releasing [[histamine]]; at higher concentrations it displays anti-inflammatory activities <ref>{{cite journal |last1=Dreyer |first1= F |year= 1990 |title= Peptide Toxins and potassium channels |journal= Rev. Physiol. Biochem. Pharmacol |volume= 115 |issue= |pages= |url= |doi= }}</ref>.


Through its effect on ionic channels, MCD peptide can induce [[long term potentiation]] ([[LTP]]) in CA1 region of hippocampus <ref>{{cite journal |last1=Cherubini |first1= E |last2= Ben Ari |first2= Y |last3= Gho |first3= M |last4= Bidard |first4= JN |last5= Lazdunski |first5= M |year= 1987 |title= Long-term potentiation of synaptic transmission in the hippocampus induced by a bee venom peptide |journal= Nature |volume= 328 |issue= 6125 |pages= 70–3 |url= |doi= }}</ref>. It binds and inactivates voltage-dependent K+ channels, including fast-inactivating (A-type) and slow-inactivating (delayed rectifier) K+ channels. The binding site of the MCD peptide on the K+ ion channel protein complex is a [[multimeric protein]], consisting of [[polypeptide chains]] of molecular weight between 76,000-80,000 and 38,000 Daltons <ref>{{cite journal |last1= Rehm |first1= H |last2= Lazdunski |first2= M |year=1988 |title= Purification and subunit structure of a putative K+-channel protein identified by its binding properties for dendrotoxin I |journal= Proc Natl Acad Sci |volume=85 |issue= 13 | pages=4919–23|url=|doi=}}</ref>. By blocking potassium channels, the MCD peptide can increase the duration of action potentials and increase neuronal excitability <ref>{{cite journal |last1=Dreyer |first1= F |year= 1990 |title= Peptide Toxins and potassium channels |journal= Rev. Physiol. Biochem. Pharmacol |volume= 115 |issue= |pages= |url= |doi= }}</ref>.
Through its effect on ionic channels, MCD peptide can induce [[long term potentiation]] ([[LTP]]) in CA1 region of hippocampus <ref>{{cite journal |last1=Cherubini |first1= E |last2= Ben Ari |first2= Y |last3= Gho |first3= M |last4= Bidard |first4= JN |last5= Lazdunski |first5= M |year= 1987 |title= Long-term potentiation of synaptic transmission in the hippocampus induced by a bee venom peptide |journal= Nature |volume= 328 |pmid=2885754 |issue= 6125 |pages= 70–3 |url= |doi=10.1038/328070a0 }}</ref>. It binds and inactivates voltage-dependent K+ channels, including fast-inactivating (A-type) and slow-inactivating (delayed rectifier) K+ channels. The binding site of the MCD peptide on the K+ ion channel protein complex is a [[multimeric protein]], consisting of [[polypeptide chains]] of molecular weight between 76,000-80,000 and 38,000 Daltons <ref>{{cite journal |last1= Rehm |first1= H |last2= Lazdunski |first2= M |year=1988 |title= Purification and subunit structure of a putative K+-channel protein identified by its binding properties for dendrotoxin I |journal= Proc Natl Acad Sci |volume=85 |pmid= 2455300 |issue= 13 | pages=4919–23 |pmc= 280549|url=|doi=10.1073/pnas.85.13.4919}}</ref>. By blocking potassium channels, the MCD peptide can increase the duration of action potentials and increase neuronal excitability <ref>{{cite journal |last1=Dreyer |first1= F |year= 1990 |title= Peptide Toxins and potassium channels |journal= Rev. Physiol. Biochem. Pharmacol |volume= 115 |issue= |pages= |url= |doi= }}</ref>.


== Toxicity ==
== Toxicity ==
The neurotoxicity of MCD peptide is distincted from its histamine releasing function <ref>{{cite journal |last1=Breithaupt |first1= H |last2= Habermann |first2= E |year= 1968 |title= Mastzelldegranulierendes Peptid (MCD-Peptid) aus Bienengift: Isolierung, biochemische und pharmakologische Eigenschaften |journal= Naunyn-Schmiedebergs Arch. Pharmak. exp. Path. |volume= 261 |issue= |pages= 252–270 |url= |doi= }}</ref>. The histamine releasing function of MCD peptide, at low concentrations, causes the degranulation of mast cell <ref>{{cite journal |last1= Buku |first1= A |year= 1999 |title= Mast cell degranulating (MCD) peptide: a prototypic peptide in allergy and inflammation |journal= Peptides |volume= 20 |issue= 3 |pages= 415–20 |url= |doi= }}</ref>
The neurotoxicity of MCD peptide is distincted from its histamine releasing function <ref>{{cite journal |last1=Breithaupt |first1= H |last2= Habermann |first2= E |year= 1968 |title= Mastzelldegranulierendes Peptid (MCD-Peptid) aus Bienengift: Isolierung, biochemische und pharmakologische Eigenschaften |journal= Naunyn-Schmiedebergs Arch. Pharmak. Exp. Path. |volume= 261 |issue= |pages= 252–270 |url= |doi=10.1007/BF00536989 }}</ref>. The histamine releasing function of MCD peptide, at low concentrations, causes the degranulation of mast cell <ref>{{cite journal |last1= Buku |first1= A |year= 1999 |title= Mast cell degranulating (MCD) peptide: a prototypic peptide in allergy and inflammation |journal= Peptides |volume= 20 |pmid= 10447103 |issue= 3 |pages= 415–20 |url= |doi=10.1016/S0196-9781(98)00167-3 }}</ref>
<ref>{{cite journal |last1=Cherubini |first1= E |last2= Ben Ari |first2= Y |last3= Gho |first3= M |last4= Bidard |first4= JN |last5= Lazdunski |first5= M |year= 1987 |title= Long-term potentiation of synaptic transmission in the hippocampus induced by a bee venom peptide |journal= Nature |volume= 328 |issue= 6125 |pages= 70–3 |url= |doi= }}</ref>, and shows anti-inflammatory activity at higher concentrations <ref>{{cite journal |last1= Buku |first1= A |year= 1999 |title= Mast cell degranulating (MCD) peptide: a prototypic peptide in allergy and inflammation |journal= Peptides |volume= 20 |issue= 3 |pages= 415–20 |url= |doi= }}</ref> <ref>{{cite journal |last1=Ziai |first1=M |last2=Russek |first2=S |last3=Wang |first3=H | last4=Beer |first4=B | last5=Blume |first5=A|year=1990 |title= Mast cell degranulating peptide: a multi-functional neurotoxin |journal= J Pharm Pharmacol |volume=42 |issue=7 |pages=457–461|url= |doi=}}</ref>. These actions of MCD peptide on mast cells is thought to be involved in allergic and inflammatory processes related to type I [[hypersensitivity]] reaction <ref>{{cite journal |last1= Schwartz |first1=L | year=1994 |title= Mast cells function and contents |journal= Curr. Opin. Immunol. |volume=6 |issue= | pages=91–97|url=|doi=}}</ref>.
<ref>{{cite journal |last1=Cherubini |first1= E |last2= Ben Ari |first2= Y |last3= Gho |first3= M |last4= Bidard |first4= JN |last5= Lazdunski |first5= M |year= 1987 |title= Long-term potentiation of synaptic transmission in the hippocampus induced by a bee venom peptide |journal= Nature |volume= 328 |pmid=2885754 |issue= 6125 |pages= 70–3 |url= |doi=10.1038/328070a0 }}</ref>, and shows anti-inflammatory activity at higher concentrations <ref>{{cite journal |last1= Buku |first1= A |year= 1999 |title= Mast cell degranulating (MCD) peptide: a prototypic peptide in allergy and inflammation |journal= Peptides |volume= 20 |pmid= 10447103 |issue= 3 |pages= 415–20 |url= |doi=10.1016/S0196-9781(98)00167-3 }}</ref> <ref>{{cite journal |last1=Ziai |first1=M |last2=Russek |first2=S |last3=Wang |first3=H | last4=Beer |first4=B | last5=Blume |first5=A|year=1990 |title= Mast cell degranulating peptide: a multi-functional neurotoxin |journal= J Pharm Pharmacol |volume=42 |pmid=1703229 |issue=7 |pages=457–461|url= |doi=}}</ref>. These actions of MCD peptide on mast cells is thought to be involved in allergic and inflammatory processes related to type I [[hypersensitivity]] reaction <ref>{{cite journal |last1= Schwartz |first1=L | year=1994 |title= Mast cells function and contents |journal= Curr. Opin. Immunol. |volume=6 |pmid= 8172685 |issue= 1| pages=91–97|url=|doi=10.1016/0952-7915(94)90039-6}}</ref>.


MCD peptide shows neurotoxicity by inducing epileptiform seizures in rat, when intraventricularly injected. This toxicity is caused by the blockage of [[voltage-gated potassium channels]] by the MCD peptide <ref>{{cite journal |last1=Ziai |first1=M |last2=Russek |first2=S |last3=Wang |first3=H | last4=Beer |first4=B | last5=Blume |first5=A|year=1990 |title= Mast cell degranulating peptide: a multi-functional neurotoxin |journal= J Pharm Pharmacol |volume=42 |issue=7 |pages=457–461|url= |doi=}}</ref>. However there is no toxicity of MCD administered peripherally, even at high doses <ref>{{cite journal |last1= Taylor |first1=J |last2= Bidard |first2=J
MCD peptide shows neurotoxicity by inducing epileptiform seizures in rat, when intraventricularly injected. This toxicity is caused by the blockage of [[voltage-gated potassium channels]] by the MCD peptide <ref>{{cite journal |last1=Ziai |first1=M |last2=Russek |first2=S |last3=Wang |first3=H | last4=Beer |first4=B | last5=Blume |first5=A|year=1990 |title= Mast cell degranulating peptide: a multi-functional neurotoxin |journal= J Pharm Pharmacol |volume=42 |pmid=1703229 |issue=7 |pages=457–461|url= |doi=}}</ref>. However there is no toxicity of MCD administered peripherally, even at high doses <ref>{{cite journal |last1= Taylor |first1=J |last2= Bidard |first2=J
| last3= Lazdunski |first3= M |year=1984|title= The characterization of high affinity binding sites in rat brain for the mast cell degranulating peptide from bee venom using purified monoiodinated peptide |journal= J Biol Chem |volume=259 |issue=2 |pages=13957–13967|url= |doi=}}</ref>.
| last3= Lazdunski |first3= M |year=1984|title= The characterization of high affinity binding sites in rat brain for the mast cell degranulating peptide from bee venom using purified monoiodinated peptide |journal= J Biol Chem |volume=259 |issue=2 |pages=13957–13967|url= |doi=}}</ref>.


== Therapeutic use ==
== Therapeutic use ==
As a mast cell activator, the MCD peptide evokes large increases in antigen-specific serum [[immunoglobulin G]] ([[IgG]]) responses <ref>{{cite journal |last1= McLachlan |first1=J |last2= Shelburne |first2=C |last3= Hart |first3=J | last4= Pizzo |first4=S | last5= Goyal |first5=R| last6= Brooking-Dixon |first6=R| last7= Staats |first7=H | last8= Abraham |first8=S | year=2008 |title= Mast cell activators: a new class of highly effective vaccine adjuvants |journal= Nat Med. |volume=14 |issue= 5| pages=536–41|url= |doi=}}</ref>. Therefore, it is used as a vaccine adjuvant. MCD peptide analogs, such as [Ala12] MCD, provide a base for designing agents that can prevent IgE/Fc-RIa interactions and reduce allergic conditions <ref>{{cite journal |last1=Buku |first1= A |last2= Condie |first2= BA |last3= Price |first3= JA |last4= Mezei |first4= M |year= 2005 |title= [Ala12]MCD peptide: a lead peptide to inhibitors of immunoglobulin E binding to mast cell receptors |journal= J Pept Res |volume= 66 |issue= 3 |pages= 132–137 |url= |doi= }}</ref> <ref>{{cite journal |last1=Buku |first1= A |last2= Priceb |first2= JA |last3= Mendlowitzc |first3= M |last4= Masurd |first4= S |year= 2001 |title= Mast cell degranulating peptide binds to RBL-2H3 mast cell receptors and inhibits IgE binding |journal= Peptides |volume= 22 |issue= |pages= 1993–1998 |url= |doi= }}</ref>.
As a mast cell activator, the MCD peptide evokes large increases in antigen-specific serum [[immunoglobulin G]] ([[IgG]]) responses <ref>{{cite journal |last1= McLachlan |first1=J |last2= Shelburne |first2=C |last3= Hart |first3=J | last4= Pizzo |first4=S | last5= Goyal |first5=R| last6= Brooking-Dixon |first6=R| last7= Staats |first7=H | last8= Abraham |first8=S | year=2008 |title= Mast cell activators: a new class of highly effective vaccine adjuvants |journal= Nat Med. |volume=14 |pmid= 18425129 |issue= 5| pages=536–41|url= |doi=10.1038/nm1757}}</ref>. Therefore, it is used as a vaccine adjuvant. MCD peptide analogs, such as [Ala12] MCD, provide a base for designing agents that can prevent IgE/Fc-RIa interactions and reduce allergic conditions <ref>{{cite journal |last1=Buku |first1= A |last2= Condie |first2= BA |last3= Price |first3= JA |last4= Mezei |first4= M |year= 2005 |title= [Ala12]MCD peptide: a lead peptide to inhibitors of immunoglobulin E binding to mast cell receptors |journal= J Pept Res |volume= 66 |pmid=16083440 |issue= 3 |pages= 132–137 |url= |doi=10.1111/j.1399-3011.2005.00281.x }}</ref> <ref>{{cite journal |last1=Buku |first1= A |last2= Priceb |first2= JA |last3= Mendlowitzc |first3= M |last4= Masurd |first4= S |year= 2001 |title= Mast cell degranulating peptide binds to RBL-2H3 mast cell receptors and inhibits IgE binding |journal= Peptides |volume= 22 |pmid=11786182 |issue= 12|pages= 1993–1998 |url= |doi=10.1016/S0196-9781(01)00542-3 }}</ref>.


==References==
==References==

Revision as of 20:30, 3 December 2010

The amino acid sequence of MCD peptide [1]
Met - Cys - Ile - Cys - Lys - Asn - Gly - Lys - Pro - Leu - Pro - Gly - Phe - Ile - Gly - Lys - Ile - Cys - Arg - Lys - Ile - Cys - Met - Met - Gln - Gln -Thr - His(NH2)

Mast cell degranulating (MCD) peptide is a cationic 22-amino acid residue peptide, which is a component of the venom of the bumblebee (Megabombus pennsylvanicus). At low concentrations, MCD peptide can stimulate mast cell degranulation. At higher concentrations, it has anti-inflammatory propterties. In addition, it is a potent blocker of voltage-sensitive potassium channels.

Source

MCD peptide is a component of bumblebee (Megabombus pennsylvanicus) venom [2]. In addition to MCD peptide, melittin and apamin have also been identified in this venom and are also described as voltage-dependent channel blockers. MCD peptide is also present in the venom of the honey bee Apis mellifera [3].

Chemistry

MCD peptide is a cationic 22-amino acid residue peptide with two disulfide bridges [4]. Although the MCD peptide sequence shows similarity with apamin [5], they have different toxic properties. MCD peptide belongs to a large family composed of numerous derivatives detecting specific targets and displaying different toxic effects [6].

Targets

MCD peptide has immunotoxic as well as neurotoxic properties due to different active sites of the MCD peptide [7]. The MCD peptide has an immunotoxic effect on mast cells [8] by releasing histamine from these cells [9]. MCD peptide has also been described as a potent modulator of voltage-gated ionic channels. It binds to several subclasses of voltage-gated potassium channels (Kv channels), including Kv1.1, Kv1.6, and less potently to Kv1.2 [10] [11] [12] [13]. Accordingly, MCD peptide can act in various regions of rat brain, including cerebellum, brainstem, hypothalamus, striatum, midbrain, cortex [14] [15], and hippocampus [16]. However, MCD peptide shows no binding activity in the peripheral neuronal system [17].

Mode of action

For its immunotoxic properties, a low concentration of MCD peptide can cause mast cell degranulation by releasing histamine; at higher concentrations it displays anti-inflammatory activities [18].

Through its effect on ionic channels, MCD peptide can induce long term potentiation (LTP) in CA1 region of hippocampus [19]. It binds and inactivates voltage-dependent K+ channels, including fast-inactivating (A-type) and slow-inactivating (delayed rectifier) K+ channels. The binding site of the MCD peptide on the K+ ion channel protein complex is a multimeric protein, consisting of polypeptide chains of molecular weight between 76,000-80,000 and 38,000 Daltons [20]. By blocking potassium channels, the MCD peptide can increase the duration of action potentials and increase neuronal excitability [21].

Toxicity

The neurotoxicity of MCD peptide is distincted from its histamine releasing function [22]. The histamine releasing function of MCD peptide, at low concentrations, causes the degranulation of mast cell [23] [24], and shows anti-inflammatory activity at higher concentrations [25] [26]. These actions of MCD peptide on mast cells is thought to be involved in allergic and inflammatory processes related to type I hypersensitivity reaction [27].

MCD peptide shows neurotoxicity by inducing epileptiform seizures in rat, when intraventricularly injected. This toxicity is caused by the blockage of voltage-gated potassium channels by the MCD peptide [28]. However there is no toxicity of MCD administered peripherally, even at high doses [29].

Therapeutic use

As a mast cell activator, the MCD peptide evokes large increases in antigen-specific serum immunoglobulin G (IgG) responses [30]. Therefore, it is used as a vaccine adjuvant. MCD peptide analogs, such as [Ala12] MCD, provide a base for designing agents that can prevent IgE/Fc-RIa interactions and reduce allergic conditions [31] [32].

References

  1. ^ Argiolas, A; Herring, P; Pisano, JJ (1985). "Amino Acid Sequence of Bumblebee MCD Peptide: A New Mast Cell Degranulating Peptide From the Venom of the Bumblebee Megabombus pennsylvanicus". Peptides. 6 (3): 431–436. doi:10.1016/0196-9781(85)90410-3.
  2. ^ Breithaupt, H; Habermann, E (1968). "Mastzelldegranulierendes Peptid (MCD-Peptid) aus Bienengift: Isolierung, biochemische und pharmakologische Eigenschaften". Naunyn-Schmiedebergs Arch. Pharmak. Exp. Path. 261: 252–270. doi:10.1007/BF00536989.
  3. ^ Bessone, R; Martin-Eauclaire, MF; Crest, M; Mourre, C (2004). "Heterogeneous competition of Kv1 channel toxins with kaliotoxin for binding in rat brain: autoradiographic analysis". Neurochem Int. 45 (7): 1039–47. doi:10.1016/j.neuint.2004.05.006. PMID 15337303.
  4. ^ Buku, A (1999). "Mast cell degranulating (MCD) peptide: a prototypic peptide in allergy and inflammation". Peptides. 20 (3): 415–20. doi:10.1016/S0196-9781(98)00167-3. PMID 10447103.
  5. ^ Gmachl, M; Kreil, G (1995). "The precursors of the bee Venom Constituents Apamin and MCD Peptide Are Encoded by two Genes in Tandem Which Share the Same 3'- Exon". J Biol Chem. 270 (21): 12704–12708. doi:10.1074/jbc.270.21.12704. PMID 7759523.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  6. ^ Buku, A (1999). "Mast cell degranulating (MCD) peptide: a prototypic peptide in allergy and inflammation". Peptides. 20 (3): 415–20. doi:10.1016/S0196-9781(98)00167-3. PMID 10447103.
  7. ^ Dreyer, F (1990). "Peptide Toxins and potassium channels". Rev. Physiol. Biochem. Pharmacol. 115.
  8. ^ Argiolas, A; Herring, P; Pisano, JJ (1985). "Amino Acid Sequence of Bumblebee MCD Peptide: A New Mast Cell Degranulating Peptide From the Venom of the Bumblebee Megabombus pennsylvanicus". Peptides. 6 (3): 431–436. doi:10.1016/0196-9781(85)90410-3.
  9. ^ King, TP; Jim, SY; Wittkowski, KM (2003). "Inflammatory role of two venom components of yellow jackets (Vespula vulgaris): a mast cell degranulating peptide mastoparan and phospholipase A1". Int. Arch. Allergy Immunol. 131 (1): 25–32. doi:10.1159/000070431. PMID 12759486.
  10. ^ Pongs, O (1992). "Molecular biology of voltage-dependent potassium channels". Physiol. Rev. 72: 69–88.
  11. ^ Grissmer, S; Nguyen, AN; Aiyar, J; Hanson, DC; Mather, RJ; Gurman, GA; Karmilowicz, MJ; Auperin, DD; Chandy, KG (1994). "Pharmacological characterization of five cloned voltage-gated K+ channels, types Kv1.1, 1.2, 1.3, 1.5, and 3.1, stably expressed in mammalian cell lines". Mol Pharmacol. 45 (6): 1227–1234. PMID 7517498.
  12. ^ Harvey, AL (1997). "Recent studies on dendrotoxins and potassium ion channels". Gen. Pharmacol. 28 (1): 7–12. PMID 9112070.
  13. ^ Stühmer, M; Ruppersberg, J; Schröter, K; Sakmann, B; Stocker, M; Giese, K; Perschke, A; Baumann, A; Pongs, O (1989). "Molecular basis of functional diversity of voltage-gated potassium channels in mammalian brain". EMBO J. 8 (11): 3235–3244. PMC 401447. PMID 2555158.
  14. ^ Dreyer, F (1990). "Peptide Toxins and potassium channels". Rev. Physiol. Biochem. Pharmacol. 115.
  15. ^ Taylor, J; Bidard, J; Lazdunski, M (1984). "The characterization of high affinity binding sites in rat brain for the mast cell degranulating peptide from bee venom using purified monoiodinated peptide". J Biol Chem. 259 (2): 13957–13967.
  16. ^ Dreyer, F (1990). "Peptide Toxins and potassium channels". Rev. Physiol. Biochem. Pharmacol. 115.
  17. ^ Taylor, J; Bidard, J; Lazdunski, M (1984). "The characterization of high affinity binding sites in rat brain for the mast cell degranulating peptide from bee venom using purified monoiodinated peptide". J Biol Chem. 259 (2): 13957–13967.
  18. ^ Dreyer, F (1990). "Peptide Toxins and potassium channels". Rev. Physiol. Biochem. Pharmacol. 115.
  19. ^ Cherubini, E; Ben Ari, Y; Gho, M; Bidard, JN; Lazdunski, M (1987). "Long-term potentiation of synaptic transmission in the hippocampus induced by a bee venom peptide". Nature. 328 (6125): 70–3. doi:10.1038/328070a0. PMID 2885754.
  20. ^ Rehm, H; Lazdunski, M (1988). "Purification and subunit structure of a putative K+-channel protein identified by its binding properties for dendrotoxin I". Proc Natl Acad Sci. 85 (13): 4919–23. doi:10.1073/pnas.85.13.4919. PMC 280549. PMID 2455300.
  21. ^ Dreyer, F (1990). "Peptide Toxins and potassium channels". Rev. Physiol. Biochem. Pharmacol. 115.
  22. ^ Breithaupt, H; Habermann, E (1968). "Mastzelldegranulierendes Peptid (MCD-Peptid) aus Bienengift: Isolierung, biochemische und pharmakologische Eigenschaften". Naunyn-Schmiedebergs Arch. Pharmak. Exp. Path. 261: 252–270. doi:10.1007/BF00536989.
  23. ^ Buku, A (1999). "Mast cell degranulating (MCD) peptide: a prototypic peptide in allergy and inflammation". Peptides. 20 (3): 415–20. doi:10.1016/S0196-9781(98)00167-3. PMID 10447103.
  24. ^ Cherubini, E; Ben Ari, Y; Gho, M; Bidard, JN; Lazdunski, M (1987). "Long-term potentiation of synaptic transmission in the hippocampus induced by a bee venom peptide". Nature. 328 (6125): 70–3. doi:10.1038/328070a0. PMID 2885754.
  25. ^ Buku, A (1999). "Mast cell degranulating (MCD) peptide: a prototypic peptide in allergy and inflammation". Peptides. 20 (3): 415–20. doi:10.1016/S0196-9781(98)00167-3. PMID 10447103.
  26. ^ Ziai, M; Russek, S; Wang, H; Beer, B; Blume, A (1990). "Mast cell degranulating peptide: a multi-functional neurotoxin". J Pharm Pharmacol. 42 (7): 457–461. PMID 1703229.
  27. ^ Schwartz, L (1994). "Mast cells function and contents". Curr. Opin. Immunol. 6 (1): 91–97. doi:10.1016/0952-7915(94)90039-6. PMID 8172685.
  28. ^ Ziai, M; Russek, S; Wang, H; Beer, B; Blume, A (1990). "Mast cell degranulating peptide: a multi-functional neurotoxin". J Pharm Pharmacol. 42 (7): 457–461. PMID 1703229.
  29. ^ Taylor, J; Bidard, J; Lazdunski, M (1984). "The characterization of high affinity binding sites in rat brain for the mast cell degranulating peptide from bee venom using purified monoiodinated peptide". J Biol Chem. 259 (2): 13957–13967.
  30. ^ McLachlan, J; Shelburne, C; Hart, J; Pizzo, S; Goyal, R; Brooking-Dixon, R; Staats, H; Abraham, S (2008). "Mast cell activators: a new class of highly effective vaccine adjuvants". Nat Med. 14 (5): 536–41. doi:10.1038/nm1757. PMID 18425129.
  31. ^ Buku, A; Condie, BA; Price, JA; Mezei, M (2005). "[Ala12]MCD peptide: a lead peptide to inhibitors of immunoglobulin E binding to mast cell receptors". J Pept Res. 66 (3): 132–137. doi:10.1111/j.1399-3011.2005.00281.x. PMID 16083440.
  32. ^ Buku, A; Priceb, JA; Mendlowitzc, M; Masurd, S (2001). "Mast cell degranulating peptide binds to RBL-2H3 mast cell receptors and inhibits IgE binding". Peptides. 22 (12): 1993–1998. doi:10.1016/S0196-9781(01)00542-3. PMID 11786182.
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