Effect of vasoactive intestinal peptide (VIP)-related peptides on cholinergic neurogenic and direct mucus secretion in ferret trachea in vitro

1 We investigated whether vasoactive intestinal peptide (VIP) and its relat ed peptides, pituitary adenylate cyclase activating peptide (PACAP) and sec retin, regulate cholinergic neural mucus secretion in ferret trachea in vit ro, using (SO4)-S-35 as a mucus marker. We also studied the interaction bet ween VIP and secretin on cholinergic mucus output. 2 VIP (1 and 10 mu M) increased secretion, whereas neither PACAP(1-27), PAC AP(1-38) nor secretin (up to 10 mu M) increased mucus output. In contrast, VIP, PACAP(1-27) and PACAP(1-38) concentration-dependently inhibited cholin ergic neural secretion, with an order of potency of VIP>PACAP(1-38)>PACAP(1 -27). Neither PACAP(1-27) nor PACAP(1-38) altered the secretion induced by acetylcholine (ACh). 3 Secretin increased cholinergic neural secretion with a maximal increase o f 190% at 1 mu M. This potentiation was blocked by VIP or atropine. Similar ly, secretin (1 mu M) potentiated VIP (1 mu M)induced mucus output by 160%. Secretin did not alter exogenous ACh-induced secretion. VTP vs secretin co mpetition curves suggested these two peptides were competing reversibly for the same receptor. 4 We conclude that, in ferret trachea in vitro, VIP and PACAPs inhibit chol inergic neural secretion via pre-junctional modulation of cholinergic neuro transmission. VIP and secretin compete for the same receptor, possibly a VI P, receptor, at which secretin may be a receptor antagonist.