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RVD-Hpα

From Wikipedia, the free encyclopedia

RVD-Hpα fragment of hemoglobin (pepcan-12), alpha 1
A polypeptide fragment derived from residues 92-104 (RVDPVNFKLLSH) in the human sequence
Identifiers
SymbolHBA1
CAS number1193362-76-3
NCBI gene3039
HGNC4823
OMIM141800
RefSeqNM_000558
UniProtP69905
Other data
LocusChr. 16 p13.3
Search for
StructuresSwiss-model
DomainsInterPro

RVD-Hpα (also known as RVD-hemopressin or Pepcan-12) is an endogenous neuropeptide belonging to the pepcan family of peptide endocannabinoids. It modulates cannabinoid receptor signalling and has been reported to act as a negative allosteric modulator of CB1 receptors and a positive allosteric modulator of CB2 receptors.[1][2]

Structure

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species RVD-Hpα sequence
human RVDPVNFKLLSH
mouse RVDPVNFKLLSH
rat RVDPVNFKfLSH
consensus RVDPVNFKxLSH

RVD-Hpα is a 12-amino-acid peptide with the sequence Arg-Val-Asp-Pro-Val-Asn-Phe-Lys-Leu-Leu-Ser-His. It is an N-terminally extended form of hemopressin, a nine-amino-acid peptide derived from the α1 subunit of hemoglobin.[3] The longer peptide pepcan-23 acts as a precursor and is cleaved to release pepcan-12.[4]

Function

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RVD-Hpα was originally proposed to act as a selective agonist of CB1 receptors. It is abundant in mouse brain and belongs to a class of peptide cannabinoid ligands distinct from lipid-derived endocannabinoids such as anandamide.[5] By comparison, hemopressin has been reported to act as a CB1 inverse agonist.[6]

Subsequent studies characterized RVD-Hpα and other N-terminally extended hemopressin peptides as negative allosteric modulators of CB1 receptors.[1][7] Other studies suggest that its effects on CB1 signalling depend on the tissue or experimental conditions, with positive modulatory effects reported in some models. Its effects in these models can be blocked by CB1 antagonists.[8][9][10]

RVD-Hpα also acts as a positive allosteric modulator of CB2 receptors.[4] It potentiates the effects of CB2 receptor agonists, including 2-arachidonoylglycerol (2-AG), with five- to tenfold potentiation reported in GTPγS binding and cAMP inhibition assays.[2]

In rodents, pepcan-12 is localized to noradrenergic neurons in the brain, particularly the locus coeruleus and its projections, and to the adrenal medulla.[11] Pepcan-12 and its precursor pepcan-23 have been detected in mouse brain, liver and kidney. Pepcan-12 levels increase during endotoxemia and ischemia–reperfusion injury, conditions in which CB2 signalling can have protective effects.[2]

RVD-Hpα also blocks the TRPV1 channel, a target shared with other endocannabinoid ligands, including anandamide and N-Arachidonoyl dopamine.[12]

Vd-hpα

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In contrast to RVD-Hpα which produces antagonist or inverse agonist activity at CB1 under most conditions but acts as an agonist at CB2, the shorter 11-amino acid peptide fragment VD-Hpα produces agonist effects at CB1 but has little or no activity at CB2, producing centrally mediated analgesic effects, hypothermia and increased sleep in animal studies through activation of the CB1 receptor.[13][14][15][16] Hybrid peptides combining VD-Hpα with peptide agonists for neuropeptide VF and opioid receptors have also been developed to produce dual acting compounds.[17][18]

References

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  1. 1 2 Bauer M, Chicca A, Tamborrini M, Eisen D, Lerner R, Lutz B, et al. (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): 36944–36967. doi:10.1074/jbc.M112.382481. PMC 3481297. PMID 22952224.
  2. 1 2 3 Petrucci V, Chicca A, Glasmacher S, Paloczi J, Cao Z, Pacher P, et al. (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.
  3. ↑ Heimann AS, Dale CS, Guimarães FS, Reis RA, Navon A, Shmuelov MA, et al. (February 2021). "Hemopressin as a breakthrough for the cannabinoid field". Neuropharmacology. 183 108406. doi:10.1016/j.neuropharm.2020.108406. PMC 8609950. PMID 33212113.
  4. 1 2 Glasmacher S, Gertsch J (May 2021). "Characterization of pepcan-23 as pro-peptide of RVD-hemopressin (pepcan-12) and stability of hemopressins in mice". Advances in Biological Regulation. 80 100808. doi:10.1016/j.jbior.2021.100808. PMID 33799079.
  5. ↑ Gomes I, Grushko JS, Golebiewska U, Hoogendoorn S, Gupta A, Heimann AS, et al. (September 2009). "Novel endogenous peptide agonists of cannabinoid receptors". FASEB Journal. 23 (9): 3020–3029. doi:10.1096/fj.09-132142. PMC 2735371. PMID 19380512.
  6. ↑ Heimann AS, Gomes I, Dale CS, Pagano RL, Gupta A, de Souza LL, et al. (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): 20588–20593. Bibcode:2007PNAS..10420588H. doi:10.1073/pnas.0706980105. PMC 2154475. PMID 18077343.
  7. ↑ 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.
  8. ↑ Zhang R, Lao K, Lu B, Guo H, Cheng J, Chen P, et al. (February 2021). "(m)RVD-hemopressin (α) and (m)VD-hemopressin (α) improve the memory-impairing effect of scopolamine in novel object and object location recognition tasks in mice". Peptides. 136 170442. doi:10.1016/j.peptides.2020.170442. PMID 33171279.
  9. ↑ Zhang R, He X, Cheng J, Zhang X, Han C, Liu Y, et al. (December 2023). "(m) RVD-hemopressin (α) Ameliorated Oxidative Stress, Apoptosis and Damage to the BDNF/TrkB/Akt Pathway Induced by Scopolamine in HT22 Cells". Neurotoxicity Research. 41 (6): 627–637. doi:10.1007/s12640-023-00677-w. PMID 37971633.
  10. ↑ Yuan X, Guo Y, Yi H, Hou X, Zhao Y, Wang Y, et al. (2024). "Hemoglobin α-derived peptides VD-hemopressin (α) and RVD-hemopressin (α) are involved in electroacupuncture inhibition of chronic pain". Frontiers in Pharmacology. 15 1439448. doi:10.3389/fphar.2024.1439448. PMC 11473328. PMID 39411061.
  11. ↑ 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.
  12. ↑ Suárez-Suárez C, González-Pérez S, Márquez-Miranda V, Araya-Duran I, Vidal-Beltrán I, Vergara S, et al. (September 2024). "The Endocannabinoid Peptide RVD-Hemopressin Is a TRPV1 Channel Blocker". Biomolecules. 14 (9): 1134. doi:10.3390/biom14091134. PMC 11430712. PMID 39334900.
  13. ↑ Han ZL, Fang Q, Wang ZL, Li XH, Li N, Chang XM, et al. (February 2014). "Antinociceptive effects of central administration of the endogenous cannabinoid receptor type 1 agonist VDPVNFKLLSH-OH [(m)VD-hemopressin(α)], an N-terminally extended hemopressin peptide". The Journal of Pharmacology and Experimental Therapeutics. 348 (2): 316–323. doi:10.1124/jpet.113.209866. PMID 24307201.
  14. ↑ Zheng T, Zhang T, Zhang R, Wang ZL, Han ZL, Li N, et al. (June 2017). "Pharmacological characterization of rat VD-hemopressin(α), an α-hemoglobin-derived peptide exhibiting cannabinoid agonist-like effects in mice". Neuropeptides. 63: 83–90. doi:10.1016/j.npep.2016.12.006. PMID 28010996.
  15. ↑ Zheng T, Zhang R, Zhang T, Zhang MN, Xu B, Song JJ, et al. (February 2018). "CB1 cannabinoid receptor agonist mouse VD-hemopressin(α) produced supraspinal analgesic activity in the preclinical models of pain". Brain Research. 1680: 155–164. doi:10.1016/j.brainres.2017.12.013. PMID 29274880.
  16. ↑ Xie JF, Wang LX, Ren WT, Wang C, Gao JX, Chen HL, et al. (2023). "An α-hemoglobin-derived peptide (m)VD-hemopressin (α) promotes NREM sleep via the CB1 cannabinoid receptor". Frontiers in Pharmacology. 14 1213215. doi:10.3389/fphar.2023.1213215. PMC 10347404. PMID 37456761.
  17. ↑ Xu B, Xiao J, Xu K, Zhang Q, Chen D, Zhang R, et al. (September 2020). "VF-13, a chimeric peptide of VD-hemopressin(α) and neuropeptide VF, produces potent antinociception with reduced cannabinoid-related side effects". Neuropharmacology. 175 108178. doi:10.1016/j.neuropharm.2020.108178. PMID 32544481.
  18. ↑ Xu B, Zhang Q, Chen D, Zhang M, Zhang R, Zhao W, et al. (February 2023). "OCP002, a Mixed Agonist of Opioid and Cannabinoid Receptors, Produces Potent Antinociception With Minimized Side Effects". Anesthesia and Analgesia. 136 (2): 373–386. doi:10.1213/ANE.0000000000006266. PMID 36638515.
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