Stimulation by ATP of Inositol Trisphosphate Accumulation and Calcium Mobilization in Cultured Adrenal Chromaffin Cells

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Abstract
Effects of ATP on accumulation of inositol phosphates and Ca2+ mobilization were investigated in cultured bovine adrenal chromaffin cells. When the cells were stimulated with 30 μM ATP, a rapid and transient rise in intracellular Ca2+ concentration was observed. At the same time, ATP rapidly increased accumulation of inositol phosphates. The concentration–response curve for the ATP‐induced Ca2+ mobilization was similar to that for inositol trisphosphate (IP3) accumulation. ATP exerted its maximal effects at 30 μM for either IP3 accumulation or Ca2+ mobilization. The order of the efficacy of the agonists for IP3 accumulation and Ca2+ mobilization at 100 μM was ATP > ADP > AMP ± adenosine. AMP (100 μM) and adenosine (300 μM) failed to induce IP3 accumulation and Ca2+ mobilization. Although 100 μM GTP and 100 μM UTP also induced IP3 accumulation and Ca2+ mobilization, their efficacy was less than that of ATP. CTP (100 μM) induced a slight IP3 accumulation, but it did not induce Ca2+ mobilization. Nifedipine (10 μM), a Ca2+ channel antagonist, and theophylline (100 μM), a P1‐purinergic receptor antagonist, failed to inhibit the ATP‐induced IP3 accumulation and Ca2+ mobilization. The above two cellular responses induced by ATP were also observed in the Ca2+‐depleted medium. ATP induced a rapid and transient accumulation of 1,4,5‐IP3 (5 s), followed by a slower accumulation of 1,3,4‐IP3. These results suggest that ATP induces the formation of 1,4,5‐IP3 through the P2‐purinergic receptor and consequently promotes Ca2+ mobilization from intracellular storage sites in cultured adrenal chromaffin cells.