Phospholipase C Activation by Prostacyclin Receptor Agonist in Cerebral Microvascular Smooth Muscle Cells (44462)

Abstract

The mechanism through which iloprost permits cerebral vasodilation induced by specific stimuli is incompletely understood. Previous study suggests there might be interplay between the adenylyl cyclase and phospholipase C (PLC) systems. Coupling of the prostacyclin receptor with the PLC pathway system was investigated. Iloprost, a stable prostacyclin analog, was used as a prostacyclin receptor agonist. We investigated the effects of iloprost (10^–12-10^–6 M) on inositol 1,4,5–trisphosphate (IP₃) production by piglet cerebrovascular smooth muscle cells in primary culture. Iloprost caused concentration- and time-dependent increases in IP₃ production in control cells and in cells pretreated with LiCI (to prevent further IP₃ metabolism). Iloprost treatment (10^–12 M) of cerebrovascular smooth muscle cells, in the absence and presence of 20 mM LiCI, resulted in 2-fold and 4-fold increases in the formation of IP₃, respectively. In contrast, 10^–10 M to 10^–6 M iloprost, either in the presence or absence of LiCI, induced moderate or no increase in IP₃ formation. Iloprost (10^–10-10^–12 M) strongly stimulated diacylglycerol (DAG) generation, whereas higher concentrations (10^–8 M) did not induce an increase. In conclusion, the results suggest that prostacyclin receptors on cerebromicrovascular smooth muscle can couple to PLC, generating the second messengers, IP₃ and DAG.