Involvement of vasoactive intestinal polypeptide in nicotine-induced relaxation of the rat gastric fundus

1 Nicotine-induced relaxation and release of vasoactive intestinal polypeptide (VIP)- and peptide histidine isoleucine (PHI)-like immunoreactivity (LI) were measured in longitudinal muscle strips from the rat gastric fundus. 2 Under non-cholinergic conditions (0.3 mu M atropine), nicotine (3-300 mu M) produced concentration-dependent relaxations of the 5-hydroxytryptamine (3 mu M)-precontracted strips. Under non-adrenergic non-cholinergic (NANC) conditions (0.3 mu M atropine+1 mu M phentolamine+1 mu M nadolol), relaxations induced by sub-maximal nicotine concentrations (10 and 30 mu M) Were significantly smaller, while that produced by the highest concentration used (300 mu M) was similar to that seen under non-cholinergic conditions. 3 Re-exposure to the same nicotine concentration I h later induced smaller relaxations, indicating desensitization. The reductions seen in the second responses were proportional to the concentration used. 4 Under non-cholinergic conditions, the relaxant response to 30 mu M nicotine was abolished by hexamethonium (100 mu M) and significantly reduced by tetrodotoxin (TTX, 3 mu M). The TTX-resistant component was not observed under NANC conditions. 5 NANC relaxation induced by 30 mu M nicotine was significantly reduced by a specific anti-VIP serum (approximately 35% less than that seen with normal rabbit serum): 6 Nicotine (30-300 mu M) caused significant, concentration-dependent increases in the outflow of VIP- and PHI-LI from the strips; these effects were also diminished with re-exposure. The increases in both types of immunoreactivity evoked by nicotine (300 mu M) were abolished by hexamethonium (300 mu M), TTX (3 mu M) and a calcium-free medium. 7 These findings indicate that VIP and possibly Pi-II are involved in NANC relaxation of the rat gastric fundus induced by nicotine.