CAPACITATIVE CA2-2B GLIOMA-CELLS - EVIDENCE THAT PHYSIOLOGICALLY EVOKED CA2+ ENTRY REGULATES CA2+-INHIBITABLE ADENYLYL-CYCLASE IN NONEXCITABLE CELLS( ENTRY EXCLUSIVELY INHIBITS CAMP SYNTHESIS IN C6)

Elevation of cytosolic free Ca2+ inhibits the type VI adenylyl cyclase that predominates in C6-2B cells, However, it is not known whether th ere is any selective requirement for Ca2+ entry or release for inhibit ion of cAMP accumulation to occur, In the present study, the effective ness 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 th e effect); Ca2+ release, which was substantial in some cases, was with out effect, A moderate inhibition, as was elicited by a modest degree of Ca2+ entry, could be rendered substantial in the absence of phospho diesterase inhibitors. Such conditions more closely mimic the physiolo gical situation of normal cells. These results are particularly signif icant, in demonstrating not only that Ca2+ entry mediates the inhibito ry effects of Ca2+ on cAMP accumulation, but also that diffuse elevati ons in [Ca2+](i) are ineffective in modulating cAMP synthesis, This pr operty suggests that, as with certain Ca2+-sensitive ion channels, Ca2 +-sensitive adenylyl cyclases may be functionally colocalized with Ca2 + entry channels.