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 microM atropine), nicotine (3-300 microM) produced concentration-dependent relaxations of the 5-hydroxytryptamine (3 microM)-precontracted strips. Under non-adrenergic non-cholinergic (NANC) conditions (0.3 microM atropine + 1 microM phentolamine + 1 microM nadolol), relaxations induced by sub-maximal nicotine concentrations (10 and 30 microM) were significantly smaller, while that produced by the highest concentration used (300 microM) was similar to that seen under non-cholinergic conditions. 3. Re-exposure to the same nicotine concentration 1 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 microM nicotine was abolished by hexamethonium (100 microM) and significantly reduced by tetrodotoxin (TTX, 3 microM). The TTX-resistant component was not observed under NANC conditions. 5. NANC relaxation induced by 30 microM nicotine was significantly reduced by a specific anti-VIP serum (approximately 35% less than that seen with normal rabbit serum). 6. Nicotine (30-300 microM) 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 microM) were abolished by hexamethonium (300 microM), TTX (3 microM) and a calcium-free medium. 7. These findings indicate that VIP and possibly PHI are involved in NANC relaxation of the rat gastric fundus induced by nicotine.
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Institute of Pharmacology, Catholic University School of Medicine, Rome, Italy.
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D000818:Animals; D003470:Culture Media; D005260:Female; D005748:Gastric Fundus / Q000187:drug effects* / Q000502:physiology; D007106:Immune Sera; D066298:In Vitro Techniques; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D009500:Neutralization Tests; D009538:Nicotine / Q000494:pharmacology*; D010451:Peptide PHI / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D015203:Reproducibility of Results; D014660:Vasoactive Intestinal Peptide / Q000276:immunology / Q000502:physiology*
D003470:Culture Media; D007106:Immune Sera; D010451:Peptide PHI; D014660:Vasoactive Intestinal Peptide; D009538:Nicotine