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RVD-Hpα fragment of hemoglobin (pepcan-12), alpha 1
CAS number1193362-76-3
NCBI gene3039
Other data
LocusChr. 16 p13.3
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RVD-Hpα (pepcan-12) is an endogenous neuropeptide found in human and mammalian brain, which was originally proposed to act as a selective agonist for the CB1 cannabinoid receptor. It is a 12-amino acid polypeptide having the amino acid sequence Arg-Val-Asp-Pro-Val-Asn-Phe-Lys-Leu-Leu-Ser-His and is an N-terminal extended form of hemopressin, a 9-AA polypeptide derived from the α1 subunit of hemoglobin which has previously been shown to act as a CB1 inverse agonist.[1] All three polypeptides have been isolated from various mammalian species, with RVD-Hpα being one of the more abundant neuropeptides expressed in mouse brain, and these neuropeptides represent a new avenue for cannabinoid research distinct from the previously known endogenous lipid-derived cannabinoid agonists such as anandamide.[2] Recently it was shown that RVD-Hpα (also called Pepcan-12) is a potent negative allosteric modulator at CB1 receptors, together with other newly described N-terminally extended peptides (pepcans).[3][4]

Pepcan-12 is the major peptide of a family of endogenous peptide endocannabinoids (pepcans) shown to act as negative allosteric modulators (NAM) of cannabinoid CB1 receptors. It is shown that pepcan-12 opposite acts as a potent CB2 cannabinoid receptor positive allosteric modulator (PAM). This peptide is very specifically expressed in the noradrenergic neurons in the brain, mainly the locus coeruleus and its projections and in the adrenal medulla.[5] RVD-Hpα also significantly potentiated the effects of CB2 receptor agonists, including the endocannabinoid 2-arachidonoyl glycerol (2-AG), for GTPγS binding and cAMP inhibition (5–10 fold). The putative precursor pepcan-23 was identified with pepcan-12 in brain, liver and kidney in mice,. RVD-Hpα was increased upon endotoxemia and ischemia reperfusion damage where CB2 receptors play a protective role. The wide occurrence of this endogenous hormone-like CB2 receptor PAM, with unforeseen opposite allosteric effects on cannabinoid receptors, suggests its potential role in peripheral pathophysiological processes.[6]

species RVD-Hpα sequence
consensus RVDPVNFKxLSH


  1. ^ Heimann AS, Gomes I, Dale CS, Pagano RL, Gupta A, de Souza LL, Luchessi AD, Castro LM, Giorgi R, Rioli V, Ferro ES, Devi LA (December 2007). "Hemopressin is an inverse agonist of CB1 cannabinoid receptors". Proceedings of the National Academy of Sciences of the United States of America. 104 (51): 20588–93. Bibcode:2007PNAS..10420588H. doi:10.1073/pnas.0706980105. PMC 2154475. PMID 18077343.
  2. ^ Gomes I, Grushko JS, Golebiewska U, Hoogendoorn S, Gupta A, Heimann AS, Ferro ES, Scarlata S, Fricker LD, Devi LA (September 2009). "Novel endogenous peptide agonists of cannabinoid receptors". FASEB Journal. 23 (9): 3020–9. doi:10.1096/fj.09-132142. PMC 2735371. PMID 19380512.
  3. ^ Bauer M, Chicca A, Tamborrini M, Eisen D, Lerner R, Lutz B, Poetz O, Pluschke G, Gertsch J (October 2012). "Identification and quantification of a new family of peptide endocannabinoids (Pepcans) showing negative allosteric modulation at CB1 receptors". The Journal of Biological Chemistry. 287 (44): 36944–67. doi:10.1074/jbc.M112.382481. PMC 3481297. PMID 22952224.
  4. ^ Macedonio G, Stefanucci A, Maccallini C, Mirzaie S, Novellino E, Mollica A (2016). "Hemopressin Peptides as Modulators of the Endocannabinoid System and their Potential Applications as Therapeutic Tools". Protein and Peptide Letters. 23 (12): 1045–1051. doi:10.2174/0929866523666161007152435. PMID 27748182.
  5. ^ Hofer SC, Ralvenius WT, Gachet MS, Fritschy JM, Zeilhofer HU, Gertsch J (November 2015). "Localization and production of peptide endocannabinoids in the rodent CNS and adrenal medulla". Neuropharmacology. 98: 78–89. doi:10.1016/j.neuropharm.2015.03.021. PMID 25839900. S2CID 43599023.
  6. ^ Petrucci V, Chicca A, Glasmacher S, Paloczi J, Cao Z, Pacher P, Gertsch J (August 2017). "Pepcan-12 (RVD-hemopressin) is a CB2 receptor positive allosteric modulator constitutively secreted by adrenals and in liver upon tissue damage". Scientific Reports. 7 (1): 9560. Bibcode:2017NatSR...7.9560P. doi:10.1038/s41598-017-09808-8. PMC 5573408. PMID 28842619.