Vasoactive intestinal peptide released by acetylcholine in the dog ileum

Release of vasoactive intestinal peptide (VIP) in response to acetylcholine (ACh) was characterized in the dog ileum using cholinergic antagonists. In blood-perfused ileum, ACh (2-200 nmol/min) produced a dose-dependent increase in venous VIP output, which was slightly reduced by hexamethonium (10 nmol/min) and blocked by hexamethonium and atropine (10 nmol/min) in combination. In isolated ileal tissues containing the submucous or myenteric plexus, excess KCl (75 mM), veratridine (0.1 mM) and ACh (0.1 mM) evoked the release of VIP. ACh-induced VIP output was decreased slightly by hexamethonium (0.1 mM), and blocked by atropine (0.1 mM) or pirenzepine (0.1 mM). Dimethylphenylpiperazinium (0.1 mM) also caused a small increase in VIP output sensitive to hexamethonium in the ileal tissues containing either the submucous or myenteric plexus. It is concluded that ACh evokes the release of VIP from VIP-containing neurons of the submucous and myenteric plexuses in the dog ileum mainly through the activation of M1 muscarinic receptors.