Evidence for the convergence of beta-adrenergic and muscarinic signalling systems at a post-receptor site.
The beta-adrenergic agonist isoproterenol stimulates inositol trisphosphate (IP3) formation and cytosolic Ca2+ [( Ca2+]i) mobilization in rat parotid acini via a cAMP-dependent process. Atropine, a muscarinic antagonist, inhibited these isoproterenol responses without affecting isoproterenol-induced amylase secretion or peak [Ca2+]i and IP3 responses elicited by alpha 1-adrenergic stimulation with epinephrine. Atropine had no effect on isoproterenol-induced [Ca2+]i responses in a cell line which lacked muscarinic receptors and did not alter beta-adrenoreceptor ligand binding. These results suggest that the inhibition by atropine results from a post-receptor effect on cAMP-mediated stimulation of phosphatidylinositol 4,5 bisphosphate (PIP2) hydrolysis.
Horn
V J
VJ
Clinical Investigations and Patient Care Branch, National Institute of Dental Research, Bethesda, MD 20892.
Baum
B J
BJ
Ambudkar
I S
IS
D000681:Amylases / Q000378:metabolism; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001665:Binding Sites / Q000187:drug effects; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D004837:Epinephrine / Q000494:pharmacology; D007295:Inositol Phosphates / Q000378:metabolism; D007545:Isoproterenol / Q000037:antagonists & inhibitors / Q000494:pharmacology; D010306:Parotid Gland / Q000187:drug effects / Q000378:metabolism; D019269:Phosphatidylinositol 4,5-Diphosphate; D010716:Phosphatidylinositols / Q000378:metabolism; D051381:Rats; D011943:Receptors, Adrenergic, beta / Q000187:drug effects* / Q000502:physiology; D011976:Receptors, Muscarinic / Q000187:drug effects* / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects
D007295:Inositol Phosphates; D019269:Phosphatidylinositol 4,5-Diphosphate; D010716:Phosphatidylinositols; D011943:Receptors, Adrenergic, beta; D011976:Receptors, Muscarinic; D001285:Atropine; D000681:Amylases; D007545:Isoproterenol; D002118:Calcium; D004837:Epinephrine