title: Dual effects of endothelin-1 on extracellular acidification by A7r5 smooth muscle cells.
abstract: The effect of endothelin-1 on metabolic activity of A7r5 rat aortic smooth muscle cells was studied. Endothelin-1 (pEC(50) 7.5) elicited an increase in the rate of extracellular medium acidification of the A7r5 cells. The ETA receptor antagonist BQ-123 blocked the endothelin-1 effect completely (pA(2) 7.6). Ca2+ channel blockers affected the endothelin-1 induced response in different ways: diltiazem and nifedipine partially blocked the endothelin-1 induced response, whereas verapamil did not influence this endothelin-1 induced effect. However, upon removal of verapamil an endothelin-1 dependent rise in extracellular acidification occurred, apparently reflecting the lifting of the verapamil blockade of an endothelin-1 induced process. Thus, this study shows that the complex integrated cellular responses upon ET-1 receptor activation are reflected in metabolic activity.
authors.affiliation: Department of Pharmacology, Solvay Duphar B.V., DA Weesp, the Netherlands.
authors.forename: B D
authors.initials: BD
authors.lastname: de Graeff
authors.forename: J H
authors.initials: JH
authors.lastname: Reinders
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D005110:Extracellular Space / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D009130:Muscle, Smooth / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010456:Peptides, Cyclic / Q000494:pharmacology; D010716:Phosphatidylinositols / Q000378:metabolism; D051381:Rats; D044022:Receptor, Endothelin A; D010738:Type C Phospholipases / Q000378:metabolism; D014700:Verapamil / Q000494:pharmacology
chemical_list: D002121:Calcium Channel Blockers; D015220:Calcium Channels; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D010456:Peptides, Cyclic; D010716:Phosphatidylinositols; D044022:Receptor, Endothelin A; D014700:Verapamil; D010738:Type C Phospholipases; C072247:cyclo(Trp-Asp-Pro-Val-Leu); D002118:Calcium