Bradykinin stimulates Ca2+ mobilization in NCB-20 cells leading to direct inhibition of adenylylcyclase. A novel mechanism for inhibition of cAMP production.
The modulation of neuronal adenylylcyclase by Ca2+, acting via calmodulin, is a long-established example of a positive interaction between the Ca2(+)-mobilizing and cAMP-generating systems. In the present study, concentrations of Ca2+ that stimulate brain adenylylcyclase inhibit the adenylylcyclase of NCB-20 plasma membranes. These inhibitory effects of Ca2+ have been characterized and seem to be exerted at the catalytic unit of the enzyme; they are independent of calmodulin, Gi, and phosphodiesterase. To determine whether this inhibition of adenylylcyclase by Ca2+ could occur in the intact cell, cAMP accumulation was measured in response to bradykinin. Bradykinin, which mobilizes Ca2+ in NCB-20 cells, as a consequence of stimulating inositol phosphate production, causes a transient inhibition of prostaglandin E1 stimulation of cAMP accumulation. The inhibitory action of bradykinin is attenuated significantly by treatment of cells with the cell-permeant Ca2+ chelator, 1,2-bis-(2-aminophenoxy)-ethane-N,N,N',N'-tetraacetic acid. It seems likely that the inhibition of adenylylcyclase by low concentrations of Ca2+ represents a novel means for a negative interaction between Ca2(+)-mobilizing and cAMP-generating systems.
Boyajian
C L
CL
Department of Pharmacology, University of Colorado Health Sciences Center, Denver 80262.
Garritsen
A
A
Cooper
D M
DM
D000067956:Adenylyl Cyclase Inhibitors; D000527:Alprostadil / Q000378:metabolism; D000818:Animals; D001920:Bradykinin / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D002147:Calmodulin / Q000378:metabolism; D002460:Cell Line; D000242:Cyclic AMP / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D004745:Enkephalins / Q000494:pharmacology; D007295:Inositol Phosphates / Q000096:biosynthesis; D009294:Narcotics / Q000494:pharmacology; D051381:Rats; D012965:Sodium Chloride; D014357:Trypsin
D000067956:Adenylyl Cyclase Inhibitors; D002147:Calmodulin; D004745:Enkephalins; D007295:Inositol Phosphates; D009294:Narcotics; D012965:Sodium Chloride; D000242:Cyclic AMP; D014357:Trypsin; D000527:Alprostadil; D001920:Bradykinin; D002118:Calcium