Electrical and mechanical effects of vasoactive intestinal peptide and pituitary adenylate cyclase-activating peptide in the rat colon involve different mechanisms

Abstract

This work aimed to study the effects of pituitary adenylate cyclase-activating peptide (PACAP) and vasoactive intestinal peptide (VIP) on the mechanical and electrical activity of the circular muscle of the rat colon and the mechanisms involved in such effects. Spontaneous mechanical activity was studied in vitro in an organ bath and the membrane potential was recorded using the microelectrode technique. Both VIP and PACAP (0.1 μM) caused an immediate, sustained and tetrodotoxin (1 μM)-resistant inhibition of the cyclic spontaneous mechanical activity and hyperpolarization. The small-conductance Ca 2+-activated K + channel blocker, apamin (1 μM), did not change the VIP- and PACAP-induced relaxation but reduced the hyperpolarization induced by PACAP whereas it did not change that induced by VIP. In contrast, the purinoceptor antagonist, suramin (100 μM), blocked the hyperpolarization caused by PACAP and VIP but failed to change their mechanical inhibitory effects. Moreover, the putative PACAP and VIP receptor antagonists, PACAP-(6–38) and VIP-(10–28), respectively, both 3 μM, failed to change the effects of either peptide and modified neither the inhibitory junction potential nor the relaxation induced by electrical-field stimulation. Thus, these results suggest that the mechanisms mediating relaxation are not strictly coupled to the mechanisms mediating hyperpolarization. This could be due to activation of two distinct mechanisms of action after agonist receptor interaction.