Molecular pharmacology of intracellular Ca^<2+> changes and receptor-mediated regulation of contraction in smooth muscle

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In this study pharmacological profiles of intracellular Ca^<2+> changes and receptor-mediated regulation of contraction in smooth muscle were studied. In ileal longitudinal smooth muscle from guinea pig. Two-dimensional images of Ca^<2+> oscillations were obtained at 33-msec intervals with a Ca^<2+>-sensitive fluorescence probe, fluo-3 using the intensified CCD camera. Nicardipine (10^<-7> M) significantly decreased the maximum level of fluorescence intensity of the Ca^<2+> oscillations, inhibited the frequency of the oscillations, and tended to decrease the basal level of fluorescence intensity. However, tetrodotoxin (3 X 10^<-7> M) did not affect these oscillations. Phorbol 12, 13-dibutyrate (10^<-7> M) significantly increased the maximum level of fluorescence intensity and the frequency of Ca^<2+> oscillations, and changed them to steady and chronometric Ca^<2+> oscillations. Cyclopiazonic acid (3 X 10^<-5> M) also significantly increased the frequency of Ca^<2+> oscillations. Acetylcholine (10^<-8> M) increased the basal and maximum level of fluorescence intensity and the frequency of Ca^<2+> oscillations, and accelerated their on set. The increase of basal level of fluorescence intensity was then decreased by cyclopiazonic acid treatment. These results suggest that the augmentation of Ca^<2+> oscillations is mainly due to the activation of L-type Ca^<2+> channels, which is modulated by protein kinase C, and that the emptying of intracellular Ca^<2+> stores may activate the Ca^<2+> oscillations mediated through the increase of Ca^<2+> influx in ileal smooth muscle of guinea pig.