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

Abstract

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 (10−12–10−6M) 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 LiCl (to prevent further IP3 metabolism). Iloprost treatment (10−12M) of cerebrovascular smooth muscle cells, in the absence and presence of 20 mM LiCl, resulted in 2‐fold and 4‐fold increases in the formation of IP3, respectively. In contrast, 10−10M to 10−6M iloprost, either in the presence or absence of LiCl, induced moderate or no increase in IP3 formation. Iloprost (10−10–10−12M) strongly stimulated diacylglycerol (DAG) generation, whereas higher concentrations (10−8M) 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.

Modeling Hypertrophic IP3 Transients in the Cardiac Myocyte

“…A published report (32) of a ;30 nM peak in IP3 on stimulation by 100 nM of ET-1, together with estimates of the peak-to-basal ratio of ;2:1 (33,34), suggest that the basal concentration of IP3 in the mammalian myocyte is ;15 nM. This is the estimate used in this model.…”