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

This work aimed to study the effects of pituitary adenylate cyclase-activat ing peptide (PACAP) and vasoactive intestinal peptide (VIP) on the mechanic al and electrical activity of the circular muscle of the rat colon and the mechanisms involved in such effects. Spontaneous mechanical activity was st udied in vitro in an organ bath and the membrane potential was recorded usi ng the microelectrode technique. Both VIP and PACAP (0.1 mu M) caused an im mediate, sustained and tetrodotoxin (1 mu M)-resistant inhibition of the cy clic spontaneous mechanical activity and hyperpolarization. The small-condu ctance Ca2+-activated K+ channel blocker, apamin (1 mu M), did not change t he VIP- and PACAP-induced relaxation but reduced the hyperpolarization indu ced by PACAP whereas it did not change that induced by VIP. In contrast, th e purinoceptor antagonist, suramin (100 mu M), blocked the hyperpolarizatio n 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 mu M, failed to change the effe cts of either peptide and modified neither the inhibitory junction potentia l nor the relaxation induced by electrical-field stimulation. Thus, these r esults suggest that the mechanisms mediating relaxation are not strictly co upled to the mechanisms mediating hyperpolarization. This could be due to a ctivation of two distinct mechanisms of action after agonist receptor inter action. (C) 2000 Elsevier Science B.V. All rights reserved.