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

Abstract

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 Ca 2+, however, the contractile response in Ca 2+-free medium was depressed by 67% ( P<0.05). The initial increase of either inositol monophosphate (InsP 1) or inositol bisphosphate (InsP 2) was not apparent, although a significant rise in both InsP 1 and InsP 2 was observed at 30 min (107 and 100% over basal level, P<0.05). The generation of inositol trisphosphate (InsP 3) 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-HT 2A receptor antagonist. A temporal study revealed that the generation of InsP 3 coincided with the phasic component of the contractile response induced by 5-hydroxytryptamine. Our results suggest that through activation of 5-HT 2A receptors, the generation of InsP 3 plays a critical role in the contraction induced by 5-hydroxytryptamine in the ovine umbilical artery.