5-HT induces an arachidonic acid-sensitive calcium influx in rat small intrapulmonary artery.
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 <250 microm) from rat. Digital imaging with fura-PE3 was used to record intracellular calcium concentration ([Ca(2+)](i)) and to follow external diameter of the vessels. 5-HT induced a sustained [Ca(2+)](i) variation that was sensitive to the inhibitor of the 5-HT(2A) 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 Ca(2+)-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.
Guibert
Christelle
C
Laboratoire de Physiologie Cellulaire Respiratoire, Institut National de la Santé et se la Recherche Médicale, Université Bordeaux 2, 146, rue Léo Saignat, 33076 Bordeaux Cedex, France. christelle.guibert@u-bordeaux2.fr
Marthan
Roger
R
Savineau
Jean-Pierre
JP
D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D020746:Calcium Channels, L-Type / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology; D016166:Free Radical Scavengers / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D008833:Microcirculation; D011651:Pulmonary Artery / Q000187:drug effects* / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology
D020746:Calcium Channels, L-Type; D016166:Free Radical Scavengers; D016718:Arachidonic Acid; D012701:Serotonin; D002118:Calcium