J. Biochem, 1988, Vol. 104, No. 5 795-800
© 1988 Japanese Biochemical Society
research-article |
Cyclic AMP Enhances Inositol Trisphosphate-Induced Mobilization of Intracellular Ca2+ in Cultured Aortic Smooth Muscle Cells1
Department of Molecular Physiology, National Cardiovascular Center Research Institute Suita, Osaka 565
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.
1 This work was supported by a Research Grant for Cardiovascular Diseases (62A-1) from the Ministry of Health and Welfare and a Grant-in-Aid for Scientific Research from the Ministry of Education, Science and Culture of Japan.