title: Intracellular Ca2+ elevation and contraction due to prostaglandin F2alpha in rat aorta.
abstract: Prostaglandin F2alpha was tested to determine (a) whether its effect on intracellular Ca2+ levels ([Ca2+]i) and force in vascular smooth muscle was mediated through activation of the thromboxane A2 and/or prostaglandin receptor, and (b) the relative roles of Ca2+ influx via L-type and non-L-type Ca2+ channels in prostaglandin receptor-mediated contraction. [Ca2+]i and force were measured simultaneously in fura-2-loaded rat aortic strips. The thromboxane A2 receptor antagonist, SQ29548 ([1S]-1a,2b(5Z),3b,4a-7-(3-[2-[(phenylamino)carbonyl] hydrazinomethyl)-7-oxobicyclo-[2.2.1]hept-2-yl-5-heptenoic acid), prevented the prostaglandin F2alpha-induced plateau [Ca2+]i elevation and force by 80-90%, while abolishing these responses due to the thromboxane A2 receptor agonist, U46619 (9,11-dideoxy-9alpha,11alpha-methanoepoxy prostaglandin F2alpha). Prostaglandin F2alpha (+ SQ29548)-induced plateau [Ca2+]i elevation and force were not inhibited by verapamil. Ni2+, a non-selective cation channel blocker, in the presence of verapamil, abolished the prostaglandin F2alpha (+ SQ29548)-elevated [Ca2+]i, while the contraction was only partially inhibited. These results suggest that, in rat aorta, (1) elevated [Ca2+]i and force due to high prostaglandin F2alpha concentrations largely results from thromboxane A2 receptor activation, and (2) the prostaglandin component of the prostaglandin F2alpha-induced contraction is dependent on Ca2+ influx via non-L-type channels.
authors.affiliation: Department of Pharmacology and Cell Biophysics, University of Cincinnati, OH 45267-0575, USA.
authors.forename: M
authors.initials: M
authors.lastname: Tosun
authors.forename: R J
authors.initials: RJ
authors.lastname: Paul
authors.forename: R M
authors.initials: RM
authors.lastname: Rapoport
mesh_terms: D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism*; D019086:Bridged Bicyclo Compounds, Heterocyclic; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism; D015237:Dinoprost / Q000494:pharmacology*; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017482:Receptors, Thromboxane / Q000037:antagonists & inhibitors; D013928:Thromboxane A2 / Q000378:metabolism; D014700:Verapamil / Q000494:pharmacology
chemical_list: D019086:Bridged Bicyclo Compounds, Heterocyclic; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines; D017482:Receptors, Thromboxane; D013928:Thromboxane A2; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; C045749:SQ 29548; D015237:Dinoprost; D014700:Verapamil; D002118:Calcium