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Regional differences in anandamide- and methanandamide-induced membrane potential changes in rat mesenteric arteries.
J Pharmacol Exp Ther. 2001 Feb; 296(2):322-8.JP

Abstract

The possibility that anandamide is an endothelium-derived hyperpolarizing factor was explored in the rat mesenteric vasculature by use of conventional microelectrode techniques. In the main mesenteric artery, anandamide and its more stable analog methanandamide hardly caused a measurable change in membrane potential of the smooth muscle cells, which promptly hyperpolarized to EDHF liberated by acetylcholine. Inhibition of endogenous anandamide breakdown by phenylmethylsulfonyl fluoride did not increase membrane responses to acetylcholine. The CB(1) receptor antagonist SR141716 did not significantly influence EDHF-mediated hyperpolarization except at extremely high concentrations. Smooth muscle cells of third to fourth order branches of the mesenteric artery, which have a more negative resting membrane potential and show smaller responses to acetylcholine, hyperpolarized by about 6 mV to both anandamide and methanandamide, whereas another CB(1) receptor agonist, WIN 55,212-2, had no effect. Mechanical endothelium removal or pre-exposure to SR141716A did not affect anandamide- and methanandamide-induced hyperpolarizations. However, in the presence of capsazepine, a selective vanilloid receptor antagonist, these membrane potential changes were reversed to a small depolarization, whereas EDHF-induced hyperpolarizations were not affected. Pretreating small vessels with capsaicin, causing desensitization of vanilloid receptors and/or depletion of sensory neurotransmitter, completely blocked methanandamide-induced hyperpolarizations. These findings show that anandamide cannot be EDHF. In smooth muscle cells of small arteries, anandamide-induced changes in membrane potential are mediated by vanilloid receptors on capsaicin-sensitive sensory nerves. The different membrane response to the cannabinoids between the main mesenteric artery and its daughter branches might be explained by the different density of perivascular innervation.

Authors+Show Affiliations

Department of Physiology and Physiopathology, Ghent University, Ghent, Belgium. Bert.Vanheel@rug.ac.beNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

11160613

Citation

Vanheel, B, and J Van de Voorde. "Regional Differences in Anandamide- and Methanandamide-induced Membrane Potential Changes in Rat Mesenteric Arteries." The Journal of Pharmacology and Experimental Therapeutics, vol. 296, no. 2, 2001, pp. 322-8.
Vanheel B, Van de Voorde J. Regional differences in anandamide- and methanandamide-induced membrane potential changes in rat mesenteric arteries. J Pharmacol Exp Ther. 2001;296(2):322-8.
Vanheel, B., & Van de Voorde, J. (2001). Regional differences in anandamide- and methanandamide-induced membrane potential changes in rat mesenteric arteries. The Journal of Pharmacology and Experimental Therapeutics, 296(2), 322-8.
Vanheel B, Van de Voorde J. Regional Differences in Anandamide- and Methanandamide-induced Membrane Potential Changes in Rat Mesenteric Arteries. J Pharmacol Exp Ther. 2001;296(2):322-8. PubMed PMID: 11160613.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Regional differences in anandamide- and methanandamide-induced membrane potential changes in rat mesenteric arteries. AU - Vanheel,B, AU - Van de Voorde,J, PY - 2001/2/13/pubmed PY - 2001/4/6/medline PY - 2001/2/13/entrez SP - 322 EP - 8 JF - The Journal of pharmacology and experimental therapeutics JO - J Pharmacol Exp Ther VL - 296 IS - 2 N2 - The possibility that anandamide is an endothelium-derived hyperpolarizing factor was explored in the rat mesenteric vasculature by use of conventional microelectrode techniques. In the main mesenteric artery, anandamide and its more stable analog methanandamide hardly caused a measurable change in membrane potential of the smooth muscle cells, which promptly hyperpolarized to EDHF liberated by acetylcholine. Inhibition of endogenous anandamide breakdown by phenylmethylsulfonyl fluoride did not increase membrane responses to acetylcholine. The CB(1) receptor antagonist SR141716 did not significantly influence EDHF-mediated hyperpolarization except at extremely high concentrations. Smooth muscle cells of third to fourth order branches of the mesenteric artery, which have a more negative resting membrane potential and show smaller responses to acetylcholine, hyperpolarized by about 6 mV to both anandamide and methanandamide, whereas another CB(1) receptor agonist, WIN 55,212-2, had no effect. Mechanical endothelium removal or pre-exposure to SR141716A did not affect anandamide- and methanandamide-induced hyperpolarizations. However, in the presence of capsazepine, a selective vanilloid receptor antagonist, these membrane potential changes were reversed to a small depolarization, whereas EDHF-induced hyperpolarizations were not affected. Pretreating small vessels with capsaicin, causing desensitization of vanilloid receptors and/or depletion of sensory neurotransmitter, completely blocked methanandamide-induced hyperpolarizations. These findings show that anandamide cannot be EDHF. In smooth muscle cells of small arteries, anandamide-induced changes in membrane potential are mediated by vanilloid receptors on capsaicin-sensitive sensory nerves. The different membrane response to the cannabinoids between the main mesenteric artery and its daughter branches might be explained by the different density of perivascular innervation. SN - 0022-3565 UR - https://www.unboundmedicine.com/medline/citation/11160613/Regional_differences_in_anandamide__and_methanandamide_induced_membrane_potential_changes_in_rat_mesenteric_arteries_ L2 - https://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=11160613 DB - PRIME DP - Unbound Medicine ER -