Interaction between the calcium and cyclic AMP messenger systems in perifused rat parotid acinar cells. Possible mechanism for potentiation of amylase secretion.
Potentiation of amylase secretion induced by a combination of isoproterenol and carbamylcholine was examined in perifused rat parotid acinar cells. The time course of changes in the augmented amylase secretion induced by isoproterenol plus carbamylcholine was similar to that induced by carbamylcholine alone, but not to that caused by isoproterenol. Concentration-response analysis showed that isoproterenol increased the apparent affinity for carbamylcholine to stimulate amylase secretion with the maximum effect attained by isoproterenol plus carbamylcholine being higher than that attained by isoproterenol or carbamylcholine. 8-Bromo cyclic AMP, forskolin and 3-isobutyl-1-methylxanthine mimicked the effect of isoproterenol. Calcium ionophores (A23187 and ionomycin), but not phorbol 12,13-dibutyrate, mimicked the effect of carbamylcholine. Chelation of intracellular free calcium with 1,2-bis-[2-aminophenoxyl]-ethane-N,N,N',N'-tetraacetic acid, but not that of extracellular calcium with [ethylenebis(oxyethylenenitrile)]-tetraacetic acid (EGTA), abolished the potentiation. Calmodulin antagonists inhibited amylase secretion induced by isoproterenol plus carbamylcholine or carbamylcholine alone, but not that induced by isoproterenol alone. These results suggest that the potentiation is mainly, if not completely, caused by a coordinated interaction between the cyclic AMP system and the Ca2+ system at a step distal to second messenger generation, probably via a cyclic AMP-induced increase in the sensitivity of the Ca2+ response element to calcium.
Yoshimura
K
K
Department of Oral Physiology, Hokkaido University, School of Dentistry, Sapporo, Japan.
Nezu
E
E
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000681:Amylases / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002217:Carbachol / Q000494:pharmacology; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D010306:Parotid Gland / Q000187:drug effects / Q000378:metabolism*; D010477:Perfusion; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D010766:Phosphorylation; D051381:Rats; D011919:Rats, Inbred Strains; D015290:Second Messenger Systems; D013449:Sulfonamides / Q000494:pharmacology; D014268:Trifluoperazine / Q000494:pharmacology
D013449:Sulfonamides; D014268:Trifluoperazine; D015124:8-Bromo Cyclic Adenosine Monophosphate; D015240:Phorbol 12,13-Dibutyrate; C017967:W 7; D002217:Carbachol; D000242:Cyclic AMP; D000681:Amylases; D007545:Isoproterenol; D002118:Calcium