RVD-Hpα (pepcan-12) is an
endogenousneuropeptide found in human and mammalian brain, which was originally proposed to act as a selective
agonist for the
CB1cannabinoid 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
peripheralpathophysiological processes.[6]
^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.
PMID27748182.
^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.
PMID25839900.
S2CID43599023.