To elucidate the mechanism of cyclic nucleotides, such as adenosine 3',5'-cyclic monophosphate (cAMP) and guanosine 3',5' -cyclic monophosphate (cGMP), in the regulation of human gastric motility, we examined the effects of forskolin (FSK), isoproterenol (ISO) and sodium nitroprusside (SNP) on the spontaneous, high K(+) and acetylcholine (ACh)-induced contractions of corporal circular smooth muscle in human stomach. Gastric circular smooth muscle showed regular spontaneous contraction, and FSK, ISO and SNP inhibited its phasic contraction and basal tone in a concentration-dependent manner. High K(+) (50 mM) produced sustained tonic contraction, and ACh (10 microM) produced initial transient contraction followed by later sustained tonic contraction with superimposed phasic contractions. FSK, ISO and SNP inhibited high K(+)-induced tonic contraction and also ACh-induced phasic and tonic contraction in a reversible manner. Nifedipine (1 microM), inhibitor of voltage-dependent L-type calcium current (VDCC(L)), almost abolished ACh-induced phasic contractions. These findings suggest that FSK, ISO and SNP, which are known cyclic nucleotide stimulators, inhibit smooth muscle contraction in human stomach partly via inhibition of VDCC(L).
Keywords: Forskolin (FSK); Gastricintestinal (GI) tract; Human stomach; Isoproterenol (ISO); Relaxation; Sodium nitorprusside (SNP); Voltage-dependent L-type calcium current (VDCCL).