5-Hydroxytryptamine stimulates phosphoinositide hydrolysis and contraction in the ovine umbilical artery

5-Hydroxytryptamine-stimulated contraction and generation of inositol phosphates (InsPs) were investigated in isolated ovine umbilical artery from near term pregnant sheep. 5-Hydroxytryptamine produced a concentration-dependent contraction in the presence or absence of external Ca2+, however, the contractile response in Ca(2+)-free medium was depressed by 67% (P < 0.05). The initial increase of either inositol monophosphate (InsP1) or inositol bisphosphate (InsP2) was not apparent, although a significant rise in both InsP1 and InsP2 was observed at 30 min (107 and 100% over basal level, P < 0.05). The generation of inositol trisphosphate (InsP3) was rapid and reached its peak at 60-90 s (35% over basal level, P < 0.05), followed by a second rise at 30 min (96% over basal level, P < 0.05). The generation of InsPs stimulated by 5-hydroxytryptamine was also concentration-dependent. In agreement with previous contraction studies, the generation of InsPs stimulated by 5-hydroxytryptamine was blocked by 10 nM ketanserin, a specific 5-HT2A receptor antagonist. A temporal study revealed that the generation of InsP3 coincided with the phasic component of the contractile response induced by 5-hydroxytryptamine. Our results suggest that through activation of 5-HT2A receptors, the generation of InsP3 plays a critical role in the contraction induced by 5-hydroxytryptamine in the ovine umbilical artery.