Cyclic-AMP-dependent Ca2+ influx elicited by prostaglandin D2 in freshly isolated nonchromaffin cells from bovine adrenal medulla

1993 
Abstract We previously reported that prostaglandin D 2 (PGD 2 ) specifically elevates intracellular cyclic AMP in nonchromaffin cells isolated from bovine adrenal medulla (Biochim. Biophys. Acta (1989) 1011, 75–80). Here we again found that PGD 2 increased intracellular Ca 2+ concentration ([Ca 2+ ] i ) in freshly isolated nonchromaffin cells and investigated the cellular mechanisms of PGD 2 -induced [Ca 2+ ] i increase using the Ca 2+ indicator fura-2 and a fluorescence microscopic imaging system. Treatment of the cells with PGD 2 receptor agonists BW245C and ZK110841 resulted in both marked stimulation of cyclic AMP formation and an increase in [Ca 2+ ] i . The [Ca 2+ ] i response was also induced by bypassing of the receptor with forskolin, a direct activator of adenylate cyclase, but not by PGE 2 or PGF 2α both of which are devoid of the ability to generate cyclic AMP in the cells. These cyclic AMP and [Ca 2+ ] i responses induced by PGD 2 were completely blocked by the PGD 2 receptor antagonist BWA868C. The time-course of cyclic AMP production stimulated by PGD 2 coincided with that of the [Ca 2+ ] i increase. While the Ca 2+ -mobilizing hormone bradykinin stimulated a rapid inositol phosphate accumulation in nonchromaffin cells, PGD 2 did not stimulate it significantly. Removal of extracellular Ca 2+ markedly reduced the Ca 2+ response to PGD 2 in magnitude and duration, but did not alter the peak [Ca 2+ ] i response to bradykinin. These results demonstrate that PGD 2 receptor activation induces the increase in [Ca 2+ ] i via cyclic AMP mainly by increasing the Ca 2+ influx from the outside, unlike inositol trisphosphate which causes release of Ca 2+ from internal stores.
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