title: Role of phospholipase A(2) and myoendothelial gap junctions in melittin-induced arterial relaxation.
abstract: We have used preconstricted rings of rabbit superior mesenteric artery to investigate the contribution of phospholipase A(2) and gap junctional communication to endothelium-derived hyperpolarizing factor (EDHF)-type relaxations evoked by melittin, a polypeptide toxin known to mobilize arachidonic acid from the cell membrane. Arachidonyl trifluoromethyl ketone (30 microM), an inhibitor of the Ca(2+)-dependent phospholipase A(2), and Gap 27 (300 microM), a connexin-mimetic peptide which attenuates intercellular communication via gap junctions, both abolished the endothelium-dependent component of EDHF-type responses evoked by melittin in the presence of the NO synthase inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME, 300 microM) and the cyclooxygenase inhibitor indomethacin (10 microM). By contrast, the sulfhydryl agent thimerosal (300 nM), which amplifies EDHF activity, potentiated nitric oxide (NO)/prostanoid-independent relaxations induced by melittin. Neither arachidonyl trifluoromethyl ketone nor thimerosal modulated relaxations evoked by the peptide toxin in the absence of L-NAME and indomethacin. We conclude that melittin evokes EDHF-type relaxations through activation of the endothelial Ca(2+)-dependent phospholipase A(2) followed by the transmission of a chemical and/or electrical signal via myoendothelial gap junctions. This mechanism of vasorelaxation may be negatively regulated by NO.
authors.affiliation: Department of Diagnostic Radiology, Wales Heart Research Institute, University of Wales College of Medicine, Health Park, CF14 4XN, Cardiff, UK.
authors.forename: I R
authors.initials: IR
authors.lastname: Hutcheson
authors.forename: T M
authors.initials: TM
authors.lastname: Griffith
mesh_terms: D000818:Animals; D001685:Biological Factors / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D004730:Endothelium, Vascular / Q000502:physiology*; D017629:Gap Junctions / Q000502:physiology*; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D008555:Melitten / Q000494:pharmacology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology; D010741:Phospholipases A / Q000037:antagonists & inhibitors / Q000502:physiology*; D011817:Rabbits; D013849:Thimerosal / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D001685:Biological Factors; C067410:endothelium-dependent hyperpolarization factor; D008555:Melitten; D013849:Thimerosal; D009569:Nitric Oxide; D010741:Phospholipases A; D002118:Calcium; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin