Ca2+ potentiates corticotropin-induced, but not isoproterenol-induced, [3H]guanosine diphosphate release in rat adipocyte membranes.
EGTA abolished corticotropin (ACTH)-stimulated adenylate cyclase in rat adipocyte membranes. In contrast, the potency of guanosine triphosphate (GTP) stimulation of adenylate cyclase activated with ACTH was greater in the presence of Ca2+ (1 mmol/L). EGTA (1 mmol/L) powerfully inhibited ACTH-stimulated [3H]guanosine diphosphate (GDP) release from membranes prelabeled with [3H]GTP in the presence of isoproterenol (ISO) or ACTH, whereas Ca2+ significantly increased it. In contrast, neither EGTA nor Ca2+ affected ISO-stimulated [3H]GDP release. These data clearly show that Ca2+ is necessary for the binding of ACTH to its receptor, and that Ca2+ stimulates the interaction of the ACTH-occupied receptor with GTP-binding proteins.
Izawa
T
T
Department of Physiology and Pharmacology, Tokyo College of Pharmacy, Japan.
Mochizuki
T
T
Komabayashi
T
T
Suda
K
K
Tsuboi
M
M
D000262:Adenylyl Cyclases / Q000378:metabolism; D000273:Adipose Tissue / Q000166:cytology / Q000378:metabolism*; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D002462:Cell Membrane / Q000378:metabolism; D004357:Drug Synergism; D004533:Egtazic Acid / Q000494:pharmacology; D006153:Guanosine Diphosphate / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006160:Guanosine Triphosphate / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology*; D051381:Rats; D014316:Tritium
D014316:Tritium; D006153:Guanosine Diphosphate; D004533:Egtazic Acid; D006160:Guanosine Triphosphate; D000324:Adrenocorticotropic Hormone; D000262:Adenylyl Cyclases; D007545:Isoproterenol; D002118:Calcium