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 (VI P), a peptidergic neuromodulator in the gastrointestinal nervous syste m, were investigated in isolated muscle strips of the guinea-pig ileum . VIP induced concentration-dependent (20 nM-1-mu-M) contractions of l ongitudinal 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-cono toxin GVIA (100 nM), somatostatin (60 nM) and dynorphin (100 nM) aboli shed the effect of VIP. In most cases a small relaxation became eviden t. Desensitization to substance P in the presence of atropine prevente d VIP-induced contraction. A partial inhibition was observed in the pr esence of atropine (3-mu-M), spanitide (30-mu-M), omega-conotoxin GVIA (100 nM), beta-endorphin (265 nM), met-enkephalin (1100 nM) and a mix ture of spantide (30-mu-M) and omega-conotoxin GVIA (100 nM). The acti on of VIP was not significantly modified by guanethidine (3-mu-M) or h examethonium (150 -mu-M). In circular ileal strips VIP (10-300 nM) cau sed concentration-dependent relaxations through a direct myogenic effe ct. These results indicate that the VIP produced contractions of the g uinea-pig ileum are exclusively neurally mediated and involve a cholin ergic a noncholinergic-nonadrenergic (NANC) pathway. It is concluded t hat besides acetylcholine (Ach) VIP releases the peptidergic transmitt er substance P from postganglionic nerve fibers of myenteric plexus. O pioid peptides and somatostatin modulate the activity of cholinergic a nd peptidergic nerves in the guinea-pig ileum. The release of substanc e P appears to depend completely on N-type voltage sensitive calcium c hannels.