Effects of E-1020, a new cyclic AMP-specific phosphodiesterase inhibitor, on cyclic amp and cytosolic free calcium of cultured vascular smooth muscle cells.

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Abstract
The purpose of this study is to clarify the pharmacological effects of E-1020, a new cAMP-specific phosphodiesterase (PDE) inhibitor, on CAMP or cytosolic free calcium (Ca) of cultured vascular smooth muscle cells (VSMC). VSMC were separated from the thoracic aorta of 2- to 3-month-old Wistar Kyoto rats (WKY). CAMP was measured by using the 125I-cAMP radioimmunoasay kit. The cytosolic free Ca of VSMC was measured by using the fluorescence Ca indicator. Fura-2 / acetoxymethyl ester (Fura-2/AM). As a result. E-1020 increased the CAMP of VSMC in a dose-dependent manner, and about two fold increase in CAMP was observed by 10-4M E-1020. E-1020 decreased the cytosolic free concentration of Ca in a dose-dependent manner, and a significant decrease in cytosolic free Ca was observed by >10-6M E-1020. These effects of E-1020 on CAMP and cytosolic free Ca were enhanced in the presence of low concentration (10;<>;8M) of DL-noradrenaline. That is, a more prominent decrease in cytosolic free Ca than that of E-1020 alone was observed. Our results show that E-1020 decreases cytosolic free Ca of VSMC in parallel with increase in cAMP, and thereby suggest a potential vasodilating activity in vivo.