Biology:RVD-Hpα

From HandWiki
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

RVD-Hpα (also known as RVD-hemopressin or 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,[1] a 9-AA polypeptide derived from the α1 subunit of hemoglobin which has previously been shown to act as a CB1 inverse agonist.[2] 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.[3] 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).[4][5] However other research suggests that RVD-hemopressin may sometimes act as a positive allosteric modulator of CB1 in certain tissues or under certain conditions, and its effects can be blocked by CB1 antagonists.[6][7][8] RVD-hemopressin has also been shown to block the TRPV1 channel, which is a target shared with other endocannabinoid ligands such as anandamide and N-Arachidonoyl dopamine.[9]

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 has more recently been discovered that pepcan-12 also acts as a potent CB2 cannabinoid receptor positive allosteric modulator (PAM), thus reducing CB1 mediated signalling while simultaneously increasing signalling mediated by CB2.[10] This peptide is specifically expressed in the noradrenergic neurons in the brain, mainly the locus coeruleus and its projections and in the adrenal medulla.[11] As a positive allosteric modulator of CB2, RVD-Hpα has been shown to significantly potentiate the effects of CB2 receptor agonists, including the endocannabinoid 2-arachidonoyl glycerol (2-AG), for GTPγS binding and cAMP inhibition (5–10 fold). The precursor pepcan-23 was identified with pepcan-12 in brain, liver and kidney in mice, and is cleaved to release pepcan-12. 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.[12]

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]

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

References

  1. ↑ Heimann, Andrea S.; Dale, Camila S.; Guimarães, Francisco S.; Reis, Ricardo A.M.; Navon, Ami; Shmuelov, Michal A.; Rioli, Vanessa; Gomes, Ivone et al. (2021). "Hemopressin as a breakthrough for the cannabinoid field". Neuropharmacology 183. doi:10.1016/j.neuropharm.2020.108406. PMID 33212113. 
  2. ↑ "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. doi:10.1073/pnas.0706980105. PMID 18077343. Bibcode: 2007PNAS..10420588H. 
  3. ↑ "Novel endogenous peptide agonists of cannabinoid receptors". FASEB Journal 23 (9): 3020–9. September 2009. doi:10.1096/fj.09-132142. PMID 19380512. 
  4. ↑ "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. doi:10.1074/jbc.M112.382481. PMID 22952224. 
  5. ↑ "Hemopressin Peptides as Modulators of the Endocannabinoid System and their Potential Applications as Therapeutic Tools". Protein and Peptide Letters 23 (12): 1045–1051. 2016. doi:10.2174/0929866523666161007152435. PMID 27748182. 
  6. ↑ Zhang, Ruisan; Lao, Kejing; Lu, Baiyu; Guo, Huifang; Cheng, Jianghong; Chen, Peng; Gou, Xingchun (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. doi:10.1016/j.peptides.2020.170442. PMID 33171279. 
  7. ↑ Zhang, R; He, X; Cheng, J; Zhang, X; Han, C; Liu, Y; Chen, P; Wang, Y (2023). "(m) RVD-hemopressin (α) Ameliorated Oxidative Stress, Apoptosis and Damage to the BDNF/TrkB/Akt Pathway Induced by Scopolamine in HT22 Cells". Neurotox Res 41: 627–637. doi:10.1007/s12640-023-00677-w. PMID 37971633. 
  8. ↑ Yuan, Xiaocui; Guo, Yixiao; Yi, Huiyuan; Hou, Xuemei; Zhao, Yulong; Wang, Yuying; Jia, Hong; Baba, Sani Sa'idu 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. doi:10.3389/fphar.2024.1439448. PMID 39411061. 
  9. ↑ Suárez-Suárez, Constanza; González-Pérez, Sebastián; Márquez-Miranda, Valeria; Araya-Duran, Ingrid; Vidal-Beltrán, Isabel; Vergara, Sebastián; Carvacho, Ingrid; Hinostroza, Fernando (2024). "The Endocannabinoid Peptide RVD-Hemopressin is a TRPV1 Channel Blocker". Biomolecules 14 (9): 1134. doi:10.3390/biom14091134. PMID 39334900. 
  10. ↑ Glasmacher, Sandra; Gertsch, Jürg (2021). "Characterization of pepcan-23 as pro-peptide of RVD-hemopressin (Pepcan-12) and stability of hemopressins in mice". Advances in Biological Regulation 80. doi:10.1016/j.jbior.2021.100808. PMID 33799079. 
  11. ↑ "Localization and production of peptide endocannabinoids in the rodent CNS and adrenal medulla". Neuropharmacology 98: 78–89. November 2015. doi:10.1016/j.neuropharm.2015.03.021. PMID 25839900. 
  12. ↑ "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). August 2017. doi:10.1038/s41598-017-09808-8. PMID 28842619. Bibcode: 2017NatSR...7.9560P. 
  13. ↑ Han, Z. L.; Fang, Q.; Wang, Z. L.; Li, X. H.; Li, N.; Chang, X. M.; Pan, J. X.; Tang, H. Z. et al. (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, Z. L.; Han, Z. L.; Li, N.; Li, X. H.; Zhang, M. N. et al. (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, M. N.; Xu, B.; Song, J. J.; Li, N.; Tang, H. H. et al. (2018). "CB(1) 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, J. F.; Wang, L. X.; Ren, W. T.; Wang, C.; Gao, J. X.; Chen, H. L.; Zhao, X. Q.; Ren, Y. L. et al. (2023). "An α-hemoglobin-derived peptide (M)VD-hemopressin (α) promotes NREM sleep via the CB(1) cannabinoid receptor". Frontiers in Pharmacology 14. doi:10.3389/fphar.2023.1213215. PMID 37456761. 
  17. ↑ Xu, B.; Xiao, J.; Xu, K.; Zhang, Q.; Chen, D.; Zhang, R.; Zhang, M.; Zhu, H. et al. (2020). "VF-13, a chimeric peptide of VD-hemopressin(α) and neuropeptide VF, produces potent antinociception with reduced cannabinoid-related side effects". Neuropharmacology 175. doi:10.1016/j.neuropharm.2020.108178. PMID 32544481. 
  18. ↑ Xu, B.; Zhang, Q.; Chen, D.; Zhang, M.; Zhang, R.; Zhao, W.; Qiu, Y.; Xu, K. et al. (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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