Capacitative Ca2+ entry exclusively inhibits cAMP synthesis in C6-2B glioma cells. Evidence that physiologically evoked Ca2+ entry regulates Ca(2+)-inhibitable adenylyl cyclase in non-excitable cells.
Elevation of cytosolic free Ca2+ inhibits the type VI adenylyl cyclase that predominates in C6-2B cells. However, it is not known whether there is any selective requirement for Ca2+ entry or release for inhibition of cAMP accumulation to occur. In the present study, the effectiveness of intracellular Ca2+ release evoked by three independent methods (thapsigargin, ionomycin, and UTP) was compared with the capacitative Ca2+ entry that was triggered by these treatments. In each situation, only Ca2+ entry could inhibit cAMP accumulation (La3+ ions blocked the effect); Ca2+ release, which was substantial in some cases, was without effect. A moderate inhibition, as was elicited by a modest degree of Ca2+ entry, could be rendered substantial in the absence of phosphodiesterase inhibitors. Such conditions more closely mimic the physiological situation of normal cells. These results are particularly significant, in demonstrating not only that Ca2+ entry mediates the inhibitory effects of Ca2+ on cAMP accumulation, but also that diffuse elevations in [Ca2+]i are ineffective in modulating cAMP synthesis. This property suggests that, as with certain Ca(2+)-sensitive ion channels, Ca(2+)-sensitive adenylyl cyclases may be functionally colocalized with Ca2+ entry channels.
Department of Pharmacology, University of Colorado Health Sciences Center, Denver 80262.
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Chiono
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Mahey
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Tate
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Cooper
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000378:metabolism; D000067956:Adenylyl Cyclase Inhibitors; D000262:Adenylyl Cyclases / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D000242:Cyclic AMP / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D005910:Glioma; D013729:Terpenes / Q000494:pharmacology; D019284:Thapsigargin; D014407:Tumor Cells, Cultured; D014544:Uridine Triphosphate / Q000494:pharmacology
D000067956:Adenylyl Cyclase Inhibitors; D013729:Terpenes; D019284:Thapsigargin; D000242:Cyclic AMP; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D000262:Adenylyl Cyclases; D002118:Calcium; D014544:Uridine Triphosphate