Inhibition of thapsigargin-induced calcium entry by microinjected guanine nucleotide analogues. Evidence for the involvement of a small G-protein in capacitative calcium entry.

Injection of mouse lacrimal acinar cells with the non-hydrolyzable analogue of GTP, GTP gamma S (guanosine 5'-3-O-(thio)triphosphate), caused a rapid release of intracellular calcium but failed to activate calcium entry. Injection of GTP gamma S together with the inositol 1,4,5-trisphosphate receptor inhibitor, heparin, did not induce calcium release but blocked the activation of capacitative calcium entry by thapsigargin. Injection of GDP beta S (guanosine 5'-O-(thio)diphosphate) produced similar effects. The inhibitor effects of GDP beta S were prevented if an equal concentration of GTP was included in the injection pipette. These findings suggest that one of the steps linking the depletion of intracellular calcium pools to calcium entry across the plasma membrane requires the hydrolysis of GTP and may involve a small G-protein.