Beta-1 adrenergic receptor

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Beta 1 adrenoceptor
Identifiers
AliasesADRB1_rcptIPR000507
External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

n/a

n/a

RefSeq (protein)

n/a

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Location (UCSC)n/an/a
PubMed searchn/an/a
Wikidata
View/Edit Human

The beta-1 adrenergic receptor1 adrenoceptor), also known as ADRB1, is a beta-adrenergic receptor, and also denotes the human gene encoding it.[1] It is a G-protein coupled receptor associated with the Gs heterotrimeric G-protein and is expressed predominantly in cardiac tissue.

Receptor[edit]

Actions[edit]

Actions of the β1 receptor include:

Effect/Tissue
Muscular Increase cardiac output cardiac muscle
Increase heart rate (chronotropic effect) sinoatrial node (SA node) [2]
Increase atrial contractility (inotropic effect) cardiac muscle
Increases contractility and automaticity ventricular cardiac muscle [2]
Increases conduction and automaticity atrioventricular node (AV node)[2]
Relaxation urinary bladder wall[3]
Exocrine Renin release juxtaglomerular cells.[2]
stimulate viscous, amylase-filled secretions

salivary glands[4]

Other Lipolysis adipose tissue.[2]

The receptor is also present in the cerebral cortex.

Agonists[edit]

Isoprenaline has higher affinity for β1 than adrenaline, which, in turn, binds with higher affinity than noradrenaline at physiologic concentrations. Selective agonists to the beta-1 receptor are:

Antagonists[edit]

(Beta blockers) β1-selective antagonists include:

Mechanism in cardiac myocytes[edit]

Gs exerts its effects via two pathways. Firstly, it directly opens L-type calcium channels (LTCC) in the plasma membrane. Secondly, it renders adenylate cyclase activated, resulting in an increase of cAMP, activating protein kinase A (PKA) which in turn phosphorylates several targets, such as phospholamban, LTCC, Troponin I (TnI), and potassium channels. Phospholamban's phosphorylation deactivates its function which is normally inhibition of SERCA on the sarcoplasmic reticulum (SR) in cardiac myocytes. Due to this, more calcium enters the SR and is therefore available for the next contraction. LTCC phosphorylatation increases its open probability and therefore allows more calcium to enter the myocyte upon cell depolarisation. Both of these mechanisms increase the available calcium for contraction and therefore increase inotropy. Conversely, TnI phosphorylation results in its facilitated dissociation of calcium from troponin C (TnC) which speeds the muscle relaxation (positive lusitropy). Potassium channel phosphorylation increases its open probability which results in shorter refractory period (because the cell repolarises faster), also increasing lusitropy. Furthermore, in nodal cells such as in the SA node, cAMP directly binds to and opens the HCN channels, increasing their open probability, which increases chronotropy.[6]

Gene[edit]

Specific polymorphisms in the ADRB1 gene have been shown to affect the resting heart rate and can be involved in heart failure.[1]

Interactions[edit]

Beta-1 adrenergic receptor has been shown to interact with DLG4[7] and GIPC1.[8] Interaction between testosterone and β-1 ARs have been shown in anxiolytic behaviors in the basolateral amygdala.[citation needed]

See also[edit]

References[edit]

  1. ^ a b "Entrez Gene: ADRB1 adrenergic, beta-1-, receptor".
  2. ^ a b c d e Fitzpatrick D, Purves D, Augustine G (2004). "Table 20:2". Neuroscience (Third ed.). Sunderland, Mass: Sinauer. ISBN 978-0-87893-725-7.
  3. ^ Moro C, Tajouri L, Chess-Williams R (January 2013). "Adrenoceptor function and expression in bladder urothelium and lamina propria". Urology. 81 (1): 211.e1–7. doi:10.1016/j.urology.2012.09.011. PMID 23200975.
  4. ^ a b c d e Rang, H. P. (2003). Pharmacology. Edinburgh: Churchill Livingstone. ISBN 978-0-443-07145-4. Page 163
  5. ^ American Society of Health-System Pharmacists, Inc. (2005-01-01). "Bisoprolol". MedlinePlus Drug Information. U.S. National Library of Medicine, National Institutes of Health. Archived from the original on 2008-05-20. Retrieved 2008-06-06.
  6. ^ Boron WF, Boulpaep EL (2012). Medical physiology : a cellular and molecular approach (Updated second ed.). Philadelphia, PA. ISBN 9781437717532. OCLC 756281854.
  7. ^ Hu LA, Tang Y, Miller WE, Cong M, Lau AG, Lefkowitz RJ, Hall RA (Dec 2000). "beta 1-adrenergic receptor association with PSD-95. Inhibition of receptor internalization and facilitation of beta 1-adrenergic receptor interaction with N-methyl-D-aspartate receptors". The Journal of Biological Chemistry. 275 (49): 38659–66. doi:10.1074/jbc.M005938200. PMID 10995758.
  8. ^ Hu LA, Chen W, Martin NP, Whalen EJ, Premont RT, Lefkowitz RJ (Jul 2003). "GIPC interacts with the beta1-adrenergic receptor and regulates beta1-adrenergic receptor-mediated ERK activation". The Journal of Biological Chemistry. 278 (28): 26295–301. doi:10.1074/jbc.M212352200. PMID 12724327.

Further reading[edit]

External links[edit]