Cyclic AMP Enhances Inositol Trisphosphate-Induced Mobilization of Intracellular Ca2+ in Cultured Aortic Smooth Muscle Cells1

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Abstract
The effect of cAMP on ATP-induced intracellular Ca+ mobilization in cultured rat aortic smooth muscle cells was investigated. Treatment of cells for 3 min at 37°C with dibutyryl cAMP, a membrane-permeable analogue of cAMP, at concentration up to 500 μM resulted in 1.5- to 1.7-fold increase in the peak cytosolic Ca2+ concentration when cells were stimulated with 3 to 200 μM ATP either in the presence or absence of extracellular Ca2+ Similar results were obtained when 0.5 mM 8-Br-cAMP or 10 μM forskolin was used instead of dibutyryl cAMP. In contrast to the Ca2+ response, dibutyryl cAMP did not affect ATP-induced formation of inositol trisphosphate (IP3) Furthermore, the dibutyryl cAMP treatment did not affect the size of the Ca2+ response elicited by 10 μM ionomycin. These results suggest that intracellular cAMP potentiates the ATP-induced Ca2+ response by enhancing Ca2+ release from the intracellular Ca2+ store(s), rather than by increasing the ATP-induced production of IP3 or by increasing the size of the intracellular Ca2+ store. Using saponinpermeabilized cells, we have shown directly that cAMP enhances Ca2+ mobilization by potentiating the Ca2+ effect of IP3 from the intracellular Ca2+ store.

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