The effects of vasoactive intestinal peptide (VIP) on contractile responses to carbachol (CCh), KCl and caffeine of the circular smooth muscle in rat stomach were examined by the isometric tension recording method and by measurement of the intracellular Ca level, [Ca]i, with fura 2. 2. Removal of extracellular Ca or nifedipine (0.1 microM) inhibited contractions induced by KCl (40 mM) and a low concentration (1 microM) of CCh but not that induced by caffeine (3 mM). After these treatments, the contraction induced by a high concentration of CCh (100 microM) changed to a phasic response. 3. VIP dose-dependently inhibited the contraction induced by 1 microM CCh, but not those caused by 40 mM KCl or 3 mM caffeine. 4. In Ca-free solution containing 2 mM EGTA, VIP inhibited the phasic contraction induced by 100 microM CCh, but not that induced by 30 mM caffeine. 5. CCh caused dose-dependent tension development concomitant with the increase in [Ca]i. VIP reduced both responses and thus did not affect the [Ca]i-force relation for CCh. In the chemically skinned muscle fibres, VIP had no effect on the pCa-tension relation. 6. It is suggested that the inhibitory effects of VIP on CCh-induced contractions are due to the inhibition of the processes of signal transduction from muscarinic receptors to voltage-dependent Ca channels and to intracellular Ca stores.
