Distinct alpha 1-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]Ins(4)P) 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 GTP gamma S- 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.
de Jonge
H W
HW
Department of Biochemistry, Faculty of Medicine and Health Sciences, Erasmus University Rotterdam, The Netherlands.
van Heugten
H A
HA
Bezstarosti
K
K
Lamers
J M
JM
D000818:Animals; D000831:Animals, Newborn; D002118:Calcium / Q000494:pharmacology; D002478:Cells, Cultured; D004075:Diglycerides / Q000378:metabolism; D016232:Endothelins / Q000494:pharmacology*; D005990:Glycerol / Q000378:metabolism; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology; D006321:Heart / Q000187:drug effects; D006352:Heart Ventricles; D007295:Inositol Phosphates / Q000302:isolation & purification / Q000378:metabolism; D007700:Kinetics; D009206:Myocardium / Q000378:metabolism*; D010656:Phenylephrine / Q000494:pharmacology*; D010716:Phosphatidylinositols / Q000378:metabolism*; D051381:Rats; D018340:Receptors, Adrenergic, alpha-1 / Q000187:drug effects / Q000502:physiology*
D004075:Diglycerides; D016232:Endothelins; D007295:Inositol Phosphates; D010716:Phosphatidylinositols; D018340:Receptors, Adrenergic, alpha-1; D010656:Phenylephrine; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D005990:Glycerol; D002118:Calcium