PT  - JOURNAL ARTICLE
AU  - Metiner Tosun
AU  - Richard J. Paul
AU  - Robert M. Rapoport
TI  - Role of Extracellular Ca<sup>++</sup> Influx <em>via</em>L-Type and Non-L-Type Ca<sup>++</sup> Channels in Thromboxane A<sub>2</sub> Receptor-Mediated Contraction in Rat Aorta
DP  - 1998 Mar 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 921--928
VI  - 284
IP  - 3
4099  - http://jpet.aspetjournals.org/content/284/3/921.short
4100  - http://jpet.aspetjournals.org/content/284/3/921.full
SO  - J Pharmacol Exp Ther1998 Mar 01; 284
AB  - 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 A2receptor-mediated contraction. In intact rat aorta, U46619, a selective thromboxane A2 receptor agonist, induced concentration-dependent increases in intracellular Ca++([Ca++]i) and contraction (EC50values of 5.5 and 6.1 nM, respectively). U46619 (10 nM) induced ∼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 ∼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++]ielevation 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. The American Society for Pharmacology and Experimental Therapeutics