5-HT induces an arachidonic acid-sensitive calcium influx in rat small intrapulmonary artery

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Abstract
5-Hydroxytryptamine (5-HT) is a potent pulmonary vasoconstrictor and contributes to hypoxic pulmonary vasoconstriction and pulmonary arterial hypertension. Small intrapulmonary vessels are very sensitive to hypoxia and play a major role for blood flow regulation in the lung. Thus we have investigated the mechanisms involved in the calcium signal to 5-HT in rat small intrapulmonary artery (IPA). Effects of 5-HT were examined in isolated IPA (external diameter 2+]i) and to follow external diameter of the vessels. 5-HT induced a sustained [Ca2+]i variation that was sensitive to the inhibitor of the 5-HT2A receptors, ketanserin, and insensitive to voltage-dependent L-type calcium channel blockers (nitrendipine and nicardipine) or voltage-independent calcium channel antagonists (LOE-908, SKF-96365, and gadolinium). The calcium response to 5-HT was also not modified by a sarcoplasmic reticulum Ca2+-ATPase inhibitor (cyclopiazonic acid; CPA), which depletes intracellular calcium stores. CPA alone activated a capacitative calcium channel that was sensitive to LOE-908 and insensitive to SKF-96365 and gadolinium. The sustained calcium signal to 5-HT was partly blocked by inhibitors of arachidonic acid production (RHC-80267 and isotetrandrine) and mimicked by application of exogenous arachidonic acid. These results suggest that activation of a noncapacitative, arachidonic acid-sensitive, receptor-operated calcium channel contributes to 5-HT-induced sustained calcium increase in small IPA.

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