RVD-Hpα explained

RVD-Hpα fragment of hemoglobin (pepcan-12), alpha 1
Caption:	A polypeptide fragment derived from residues 92-104 (RVDPVNFKLLSH) in the human sequence
Cas Number:	1193362-76-3
Hgncid:	4823
Symbol:	HBA1
Entrezgene:	3039
Omim:	141800
Refseq:	NM_000558
Uniprot:	P69905
Chromosome:	16
Arm:	p
Band:	13.3

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
human	RVDPVNFKLLSH
mouse	RVDPVNFKLLSH
rat	RVDPVNFKfLSH
consensus	RVDPVNFKxLSH

Notes and References

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 . 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 . December 2007 . 18077343 . 2154475 . 10.1073/pnas.0706980105 . 2007PNAS..10420588H . free .
2. Gomes I, Grushko JS, Golebiewska U, Hoogendoorn S, Gupta A, Heimann AS, Ferro ES, Scarlata S, Fricker LD, Devi LA . Novel endogenous peptide agonists of cannabinoid receptors . FASEB Journal . 23 . 9 . 3020–9 . September 2009 . 19380512 . 2735371 . 10.1096/fj.09-132142 . free .
3. Bauer M, Chicca A, Tamborrini M, Eisen D, Lerner R, Lutz B, Poetz O, Pluschke G, Gertsch J . 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 . October 2012 . 22952224 . 3481297 . 10.1074/jbc.M112.382481 . free .
4. Macedonio G, Stefanucci A, Maccallini C, Mirzaie S, Novellino E, Mollica A . Hemopressin Peptides as Modulators of the Endocannabinoid System and their Potential Applications as Therapeutic Tools . Protein and Peptide Letters . 23 . 12 . 1045–1051 . 2016 . 27748182 . 10.2174/0929866523666161007152435 .
5. Hofer SC, Ralvenius WT, Gachet MS, Fritschy JM, Zeilhofer HU, Gertsch J . Localization and production of peptide endocannabinoids in the rodent CNS and adrenal medulla . Neuropharmacology . 98 . 78–89 . November 2015 . 25839900 . 10.1016/j.neuropharm.2015.03.021 . 43599023 .
6. Petrucci V, Chicca A, Glasmacher S, Paloczi J, Cao Z, Pacher P, Gertsch J . 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 . August 2017 . 28842619 . 5573408 . 10.1038/s41598-017-09808-8 . 2017NatSR...7.9560P .