title: Phospholipase C activation by prostacyclin receptor agonist in cerebral microvascular smooth muscle cells.
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 LiCl (to prevent further IP3 metabolism). Iloprost treatment (10-12 M) 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, 10-10 M to 10-6 M iloprost, either in the presence or absence of LiCl, 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.
authors.affiliation: Laboratory for Research in Neonatal Physiology, Department of Physiology, The University of Tennessee, Memphis, 38163, USA.
authors.forename: P A
authors.initials: PA
authors.lastname: Parkinson
authors.forename: H
authors.initials: H
authors.lastname: Parfenova
authors.forename: C W
authors.initials: CW
authors.lastname: Leffler
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D002560:Cerebrovascular Circulation; D004075:Diglycerides / Q000378:metabolism; D019332:Endothelin-1 / Q000494:pharmacology*; D004789:Enzyme Activation; D016285:Iloprost / Q000494:pharmacology*; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D007700:Kinetics; D018021:Lithium Chloride / Q000494:pharmacology; D008833:Microcirculation; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D044006:Receptors, Epoprostenol; D011982:Receptors, Prostaglandin / Q000819:agonists*; D013552:Swine; D010738:Type C Phospholipases / Q000378:metabolism*
chemical_list: D004075:Diglycerides; D019332:Endothelin-1; D044006:Receptors, Epoprostenol; D011982:Receptors, Prostaglandin; D015544:Inositol 1,4,5-Trisphosphate; D010738:Type C Phospholipases; D018021:Lithium Chloride; D016285:Iloprost