Inhibitory actions of cilostazol on electrical responses of smooth muscle isolated from the guinea-pig stomach antrum.

We have investigated the effects of cilostazol, a type III phosphodiesterase inhibitor, on the electrical responses of smooth muscle tissue isolated from the guinea-pig stomach antrum. Cilostazol (10(-5) M) inhibited slow waves recorded from circular muscle cells, but did not significantly alter the pacemaker potentials and follower potentials recorded from myenteric interstitial cells and longitudinal muscle cells respectively. Slow potentials generated in isolated circular muscle bundles without attached myenteric interstitial cells were inhibited by cilostazol (>10(-7) M), while all membrane activities were abolished by 10(-5) M cilostazol. In circular muscle bundles, the input resistance of smooth muscle cells and the refractory period for the generation of slow potentials were not altered during the inhibition of spontaneous activity with cilostazol. While cilostazol at 10(-7) and 10(-6) M did not elevate the tissue content of cyclic AMP, at 10(-5) M cyclic AMP was elevated by about 30%. A similar elevation was also produced by 10(-7) M forskolin. The content of cyclic AMP was not significantly increased in preparations stimulated with 10(-3) M caffeine. The potency for inhibiting slow waves was in the order caffeine (10(-3) M) > forskolin (10(-7) M) > cilostazol (10(-5) M). The frequency of slow waves was decreased by caffeine or forskolin but not by cilostazol, while the duration was reduced by caffeine but not by cilostazol or forskolin. Follower potentials were modulated by caffeine and forskolin, but not by cilostazol: the duration was reduced by caffeine, the frequency was reduced by caffeine or forskolin, and the amplitude was not significantly altered by any of them. The results indicate that cilostazol has high selectivity in inhibiting the activity of circular muscle much more than that of longitudinal muscle or pacemaker cells, with no causal relation to the tissue content of cyclic AMP as appears to be the case for the inhibitory actions of caffeine and forskolin.