Distinct α1-adrenergic agonist- and endothelin-1-evoked phosphoinositide cycle responses in cultured neonatal rat cardiomyocytes

Previously it was shown by us and others in cultured neonatal rat cardiomyocytes that the desensitization of the phenylephrine (PHE)- and endothelin-1 (ET-1)-mediated response of phospholipase C (PLC) was receptor-specific. The aim of this study was to characterize receptor-dependent specificities downstream of PLC. PHE (10−4 M) as well as ET-1 (10−8 M) stimulated the total [3H]inositolphosphate ([3H]InsPn, predominantly [3H-3]Ins4P) formation to about the same extent whereas Ins(1,4,5)P3 and Ins(1,3,4,5)P4 did not increase. Yet, ET-1 but not PHE stimulated Ins(1,3,4)P3, and Ins(3,4)Pn, formation. Activation of PLC in saponin-permeabilized cells by GTPγS- and Ca2+ gave predominantly the formation of Ins(1,4)P2. The PHE- and ET-1-mediated increase of [3H]1,2-diacylglycerol was significant after respectively 16 and 8 min. PHE but not ET-1 stimulated phosphorylation of a 30 kDa protein which was likely of myofibrillar origin. It is concluded that receptor-dependent specificities exist not only at the level of PLC but also downstream