VASOACTIVE INTESTINAL POLYPEPTIDE INDUCES NEUROGENIC CONTRACTION OF GUINEA-PIG ILEUM - INVOLVEMENT OF ACETYLCHOLINE AND SUBSTANCE-P

The effect and mode of action of vasoactive intestinal polypeptide (VIP), a peptidergic neuromodulator in the gastrointestinal nervous system, were investigated in isolated muscle strips of the guinea-pig ileum. VIP induced concentration-dependent (20 nM-1-mu-M) contractions of longitudinal ileal strips. TTX (1-mu-M), a mixture of atropine (3-mu-M) and spantide (30-mu-M), a mixture of atropine (3-mu-M) and omega-conotoxin GVIA (100 nM), somatostatin (60 nM) and dynorphin (100 nM) abolished the effect of VIP. In most cases a small relaxation became evident. Desensitization to substance P in the presence of atropine prevented VIP-induced contraction. A partial inhibition was observed in the presence of atropine (3-mu-M), spanitide (30-mu-M), omega-conotoxin GVIA (100 nM), beta-endorphin (265 nM), met-enkephalin (1100 nM) and a mixture of spantide (30-mu-M) and omega-conotoxin GVIA (100 nM). The action of VIP was not significantly modified by guanethidine (3-mu-M) or hexamethonium (150 -mu-M). In circular ileal strips VIP (10-300 nM) caused concentration-dependent relaxations through a direct myogenic effect. These results indicate that the VIP produced contractions of the guinea-pig ileum are exclusively neurally mediated and involve a cholinergic a noncholinergic-nonadrenergic (NANC) pathway. It is concluded that besides acetylcholine (Ach) VIP releases the peptidergic transmitter substance P from postganglionic nerve fibers of myenteric plexus. Opioid peptides and somatostatin modulate the activity of cholinergic and peptidergic nerves in the guinea-pig ileum. The release of substance P appears to depend completely on N-type voltage sensitive calcium channels.