Role of extracellular Ca++ influx via L-type and non-L-type Ca++ channels in thromboxane A2 receptor-mediated contraction in rat aorta.
The purpose of this study was to investigate the role of extracellular Ca++ influx via L-type and non-L-type Ca++ channels in thromboxane A2 receptor-mediated contraction. In intact rat aorta, U46619, a selective thromboxane A2 receptor agonist, induced concentration-dependent increases in intracellular Ca++ ([Ca++]i) and contraction (EC50 values of 5.5 and 6.1 nM, respectively). U46619 (10 nM) induced approximately 60 to 70% of maximal [Ca++]i elevation and contraction. Treatment with verapamil, an L-type Ca++ channel blocker, before 10 nM U46619 challenge, or during the plateau [Ca++]i elevation and contraction, decreased these parameters by approximately 50%. Ni++, a nonselective blocker of cation channels, or SKF96365, a purported blocker of receptor-operated Ca++ channels, further decreased the contraction and abolished the [Ca++]i elevation that remained after verapamil treatment of 10 nM U46619-challenged vessels. Pretreatment with verapamil and Ni++ to prevent Ca++ influx and with cyclopiazonic acid to deplete [Ca++]i stores also partially prevented U46619-induced contraction, whereas [Ca++]i elevation was abolished. These results suggest that thromboxane A2 receptor-mediated contraction of vascular smooth muscle partly depends on the influx of extracellular Ca++ via both L-type and non-L-type Ca++ channels, as well as a mechanism independent of [Ca++]i elevation.
Tosun
M
M
Department of Pharmacology and Cell Biophysics, University of Cincinnati, Ohio, USA.
Paul
R J
RJ
Rapoport
R M
RM
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000502:physiology*; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000502:physiology*; D020746:Calcium Channels, L-Type; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D017482:Receptors, Thromboxane / Q000502:physiology*; D014661:Vasoconstriction; D014700:Verapamil / Q000494:pharmacology
D015220:Calcium Channels; D020746:Calcium Channels, L-Type; D017482:Receptors, Thromboxane; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D014700:Verapamil; D002118:Calcium