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Comparative pharmacology of endothelium-derived hyperpolarizing factor and anandamide in rat isolated mesentery.
Eur J Pharmacol. 1997 Aug 27; 333(2-3):191-7.EJ

Abstract

We have recently proposed that anandamide, or a related cannabinoid, is the endothelium-derived hyperpolarizing factor (EDHF) and have now compared EDHF-mediated responses (induced by carbachol in the presence of both nitric oxide and prostanoid synthesis inhibitors) with those induced by anandamide in the rat isolated superior mesenteric arterial bed. Both EDHF-mediated and anandamide-induced relaxations were inhibited in the presence of high K+ (60 mM) and opposed by blockade of K+ channels with 10 mM tetraethylammonium. The cytochrome P450 inhibitors, and putative EDHF inhibitors, clotrimazole (10 microM) and proadifen (SKF 525A) (10 microM), opposed both anandamide-induced and EDHF-mediated relaxations and also relaxant responses to the K+ channel activator levcromakalim. Therefore, EDHF-mediated and anandamide-induced vasorelaxations show very similar pharmacological characteristics, with both responses being mediated via K+ channel activation. Further, the actions of EDHF and anandamide are both sensitive to proadifen and clotrimazole, EDHF antagonists which appear to act through K+ channel inhibition. Accordingly, these results support our proposal that an endocannabinoid is an EDHF.

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Authors+Show Affiliations

Randall MD
Department of Physiology and Pharmacology, University of Nottingham Medical School, Queen's Medical Centre, UK. michael.randall@nottingham.ac.uk
McCulloch AI
No affiliation info available
Kendall DA
No affiliation info available

MeSH

AnimalsArachidonic AcidsBiological FactorsCalcium Channel BlockersCannabinoid Receptor ModulatorsCannabinoidsClotrimazoleDose-Response Relationship, DrugEndocannabinoidsEnzyme InhibitorsIn Vitro TechniquesMaleMesenteric ArteriesMuscarinic AgonistsMuscle, Smooth, VascularNG-Nitroarginine Methyl EsterPolyunsaturated AlkamidesPotassiumPotassium Channel BlockersProadifenRatsRats, WistarTetraethylammoniumVasodilationVasodilator Agents

Pub Type(s)

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

Language

eng

PubMed ID

9314035

Citation

Randall, M D., et al. "Comparative Pharmacology of Endothelium-derived Hyperpolarizing Factor and Anandamide in Rat Isolated Mesentery." European Journal of Pharmacology, vol. 333, no. 2-3, 1997, pp. 191-7.
Randall MD, McCulloch AI, Kendall DA. Comparative pharmacology of endothelium-derived hyperpolarizing factor and anandamide in rat isolated mesentery. Eur J Pharmacol. 1997;333(2-3):191-7.
Randall, M. D., McCulloch, A. I., & Kendall, D. A. (1997). Comparative pharmacology of endothelium-derived hyperpolarizing factor and anandamide in rat isolated mesentery. European Journal of Pharmacology, 333(2-3), 191-7.
Randall MD, McCulloch AI, Kendall DA. Comparative Pharmacology of Endothelium-derived Hyperpolarizing Factor and Anandamide in Rat Isolated Mesentery. Eur J Pharmacol. 1997 Aug 27;333(2-3):191-7. PubMed PMID: 9314035.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Comparative pharmacology of endothelium-derived hyperpolarizing factor and anandamide in rat isolated mesentery. AU - Randall,M D, AU - McCulloch,A I, AU - Kendall,D A, PY - 1997/8/27/pubmed PY - 1997/10/6/medline PY - 1997/8/27/entrez SP - 191 EP - 7 JF - European journal of pharmacology JO - Eur J Pharmacol VL - 333 IS - 2-3 N2 - We have recently proposed that anandamide, or a related cannabinoid, is the endothelium-derived hyperpolarizing factor (EDHF) and have now compared EDHF-mediated responses (induced by carbachol in the presence of both nitric oxide and prostanoid synthesis inhibitors) with those induced by anandamide in the rat isolated superior mesenteric arterial bed. Both EDHF-mediated and anandamide-induced relaxations were inhibited in the presence of high K+ (60 mM) and opposed by blockade of K+ channels with 10 mM tetraethylammonium. The cytochrome P450 inhibitors, and putative EDHF inhibitors, clotrimazole (10 microM) and proadifen (SKF 525A) (10 microM), opposed both anandamide-induced and EDHF-mediated relaxations and also relaxant responses to the K+ channel activator levcromakalim. Therefore, EDHF-mediated and anandamide-induced vasorelaxations show very similar pharmacological characteristics, with both responses being mediated via K+ channel activation. Further, the actions of EDHF and anandamide are both sensitive to proadifen and clotrimazole, EDHF antagonists which appear to act through K+ channel inhibition. Accordingly, these results support our proposal that an endocannabinoid is an EDHF. SN - 0014-2999 UR - https://www.unboundmedicine.com/medline/citation/9314035/Comparative_pharmacology_of_endothelium_derived_hyperpolarizing_factor_and_anandamide_in_rat_isolated_mesentery_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-2999(97)01137-0 DB - PRIME DP - Unbound Medicine ER -