HémopressineHemopressin (Hp, PVNFKFLSH)

Formula

C₅₃H₇₇N₁₃O₁₂

Molar mass

1088.30 g·mol⁻¹

CAS

568588-77-2

PubChem CID

44560117

Origin

A peptide fragment derived from haemoglobin, and not a lipid molecule like the classical endocannabinoids. Its endogenous nature is precisely the contested point: later work on the pepcan family indicates that the nonapeptide is a hydrolysis artefact produced under acidic conditions during sample preparation, and not a species genuinely present in tissues. The documented endogenous form is the longer peptide, RVD-hemopressin, described in this wiki under the name Pepcan-12.

InChIKey

DUTLYPZZJJBEAJ-QISMNGAHSA-N

Editorial estimate, not clinical.

Hemopressin is a nonapeptide of sequence PVNFKFLSH, derived from the alpha chain of haemoglobin, which has held a singular place in the history of the endocannabinoid system: that of the first peptide ligand of the CB1 receptor. Heimann and colleagues (2007) established that it binds there selectively and behaves as an inverse agonist, blocking CB1 signalling without affecting the other G protein-coupled receptors of family A, CB2 included. Antinociceptive effects have been reported in animal models of inflammatory and neuropathic pain. That history nevertheless calls for an important caveat, and this wiki states it rather than passing over it: later work on the pepcan family indicates that this nonapeptide is a hydrolysis artefact generated under acidic conditions during sample preparation, and that it does not exist as such in tissues. The genuinely endogenous endocannabinoid peptide is the extended form, RVD-hemopressin or Pepcan-12, a negative allosteric modulator of CB1 and a positive one of CB2, which is the subject of a separate entry. Hemopressin therefore remains a documented pharmacological tool whose status as a physiological mediator is not settled.

Hemopressin corresponds to residues 95 to 103 of the alpha chain of haemoglobin, released by proteolytic cleavage. It is a peptide generation route, unrelated to the lipid route that produces anandamide or 2-AG from membrane phospholipids. The status of that cleavage is debated: it occurs, as documented, under acidic extraction conditions, which raises the possibility that the peptide is generated by the method rather than by the organism.

Sources: EUR-Lex, UNODC, CND, ANSM, IUPHAR/BPS, ChEBI, EUDA. Our method.

Class

Endocannabinoid

Origin

A peptide fragment derived from haemoglobin, and not a lipid molecule like the classical endocannabinoids. Its endogenous nature is precisely the contested point: later work on the pepcan family indicates that the nonapeptide is a hydrolysis artefact produced under acidic conditions during sample preparation, and not a species genuinely present in tissues. The documented endogenous form is the longer peptide, RVD-hemopressin, described in this wiki under the name Pepcan-12.

Status

Unscheduled

1. 1.Heimann et coll. 2007 : l'hémopressine, agoniste inverse du récepteur CB1PMID 18077343
2. 2.Pepcan-12 (RVD-hémopressine), modulateur allostérique positif du CB2 (2017)PMID 28842619