TY - JOUR
T1 - Hemopressin as a breakthrough for the cannabinoid field
AU - Heimann, Andrea S.
AU - Dale, Camila S.
AU - Guimarães, Francisco S.
AU - Reis, Ricardo A.M.
AU - Navon, Ami
AU - Shmuelov, Michal A.
AU - Rioli, Vanessa
AU - Gomes, Ivone
AU - Devi, Lakshmi L.
AU - Ferro, Emer S.
N1 - ESF is a Weizmann Institute of Science (WIS) Visiting Scientist at Biological Regulation Department, supported by Erna and Jakob Michael Visiting Professorship, Rehovot, Israel. We are grateful to Dr. Natalia Szenkier Garcia for helping with the MOE platform. ESF, CSD and FSG are supported by Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP; 2016/04000-3 to ESF, 2019/06982-6 to CSD and 2017/24304-0 to FSG), and Brazilian National Research Council (CNPq; 302809/2016-3 to ESF). AN is supported by Israel Science Foundation (ISF , grant 1247/15 ), and the WIS Minerva Center. LAD is supported by NIH grants DA008863 and NS026880 . Ricardo A de Melo Reis was supported by FAPERJ (Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro) and INCT-INNT (National Institute of Translational Neuroscience 465346/2014-6 ).
PY - 2021/2/1
Y1 - 2021/2/1
N2 - Hemopressin (PVNFKFLSH in rats, and PVNFKLLSH in humans and mice), a fragment derived from the α-chain of hemoglobin, was the first peptide described to have type 1 cannabinoid receptor activity. While hemopressin was shown to have inverse agonist/antagonistic activity, extended forms of hemopressin (i.e. RVD-hemopressin, also called pepcan-12) exhibit type 1 and type 2 cannabinoid receptor agonistic/allosteric activity, and recent studies suggest that they can activate intracellular mitochondrial cannabinoid receptors. Therefore, hemopressin and hemopressin-related peptides could have location-specific and biased pharmacological action, which would increase the possibilities for fine-tunning and broadening cannabinoid receptor signal transduction. Consistent with this, hemopressins were shown to play a role in a number of physiological processes including antinociceptive and anti-inflammatory activity, regulation of food intake, learning and memory. The shortest active hemopressin fragment, NFKF, delays the first seizure induced by pilocarpine, and prevents neurodegeneration in an experimental model of autoimmune encephalomyelitis. These functions of hemopressins could be due to engagement of both cannabinoid and non-cannabinoid receptor systems. Self-assembled nanofibrils of hemopressin have pH-sensitive switchable surface-active properties, and show potential as inflammation and cancer targeted drug-delivery systems. Upon disruption of the self-assembled hemopressin nanofibril emulsion, the intrinsic analgesic and anti-inflammatory properties of hemopressin could help bolster the therapeutic effect of anti-inflammatory or anti-cancer formulations. In this article, we briefly review the molecular and behavioral pharmacological properties of hemopressins, and summarize studies on the intricate and unique mode of generation and binding of these peptides to cannabinoid receptors. Thus, the review provides a window into the current status of hemopressins in expanding the repertoire of signaling and activity by the endocannabinoid system, in addition to their new potential for pharmaceutic formulations.
AB - Hemopressin (PVNFKFLSH in rats, and PVNFKLLSH in humans and mice), a fragment derived from the α-chain of hemoglobin, was the first peptide described to have type 1 cannabinoid receptor activity. While hemopressin was shown to have inverse agonist/antagonistic activity, extended forms of hemopressin (i.e. RVD-hemopressin, also called pepcan-12) exhibit type 1 and type 2 cannabinoid receptor agonistic/allosteric activity, and recent studies suggest that they can activate intracellular mitochondrial cannabinoid receptors. Therefore, hemopressin and hemopressin-related peptides could have location-specific and biased pharmacological action, which would increase the possibilities for fine-tunning and broadening cannabinoid receptor signal transduction. Consistent with this, hemopressins were shown to play a role in a number of physiological processes including antinociceptive and anti-inflammatory activity, regulation of food intake, learning and memory. The shortest active hemopressin fragment, NFKF, delays the first seizure induced by pilocarpine, and prevents neurodegeneration in an experimental model of autoimmune encephalomyelitis. These functions of hemopressins could be due to engagement of both cannabinoid and non-cannabinoid receptor systems. Self-assembled nanofibrils of hemopressin have pH-sensitive switchable surface-active properties, and show potential as inflammation and cancer targeted drug-delivery systems. Upon disruption of the self-assembled hemopressin nanofibril emulsion, the intrinsic analgesic and anti-inflammatory properties of hemopressin could help bolster the therapeutic effect of anti-inflammatory or anti-cancer formulations. In this article, we briefly review the molecular and behavioral pharmacological properties of hemopressins, and summarize studies on the intricate and unique mode of generation and binding of these peptides to cannabinoid receptors. Thus, the review provides a window into the current status of hemopressins in expanding the repertoire of signaling and activity by the endocannabinoid system, in addition to their new potential for pharmaceutic formulations.
U2 - https://doi.org/10.1016/j.neuropharm.2020.108406
DO - https://doi.org/10.1016/j.neuropharm.2020.108406
M3 - مقالة مرجعية
C2 - 33212113
SN - 0028-3908
VL - 183
JO - Neuropharmacology
JF - Neuropharmacology
M1 - 108406
ER -