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

Abstract

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 μM atropine), nicotine (3–300 μM) produced concentration-dependent relaxations of the 5-hydroxytryptamine (3 μM)-precontracted strips. Under non-adrenergic non-cholinergic (NANC) conditions (0.3 μM atropine+1 μM phentolamine+1 μM nadolol), relaxations induced by sub-maximal nicotine concentrations (10 and 30 μM) were significantly smaller, while that produced by the highest concentration used (300 μM) 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 μM nicotine was abolished by hexamethonium (100 μM) and significantly reduced by tetrodotoxin (TTX, 3 μM). The TTX-resistant component was not observed under NANC conditions.

5. NANC relaxation induced by 30 μM nicotine was significantly reduced by a specific anti-VIP serum (approximately 35% less than that seen with normal rabbit serum).

6. Nicotine (30–300 μM) 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 μM) were abolished by hexamethonium (300 μM), TTX (3 μM) 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.

Full Text

The Full Text of this article is available as a PDF (379.4 KB).