VASOACTIVE INTESTINAL POLYPEPTIDE - A NEUROTRANSMITTER FOR LOWER ESOPHAGEAL SPHINCTER RELAXATION

The effect of rabbit vasoactive intestinal polypeptide (VIP) antiserum on in vitro relaxation of the lower esophageal sphincter (LES) was studied in 10 cats. The stomach and esophagus were opened along the lesser curvature of the stomach and stripped of mucosa. Consecutive strips were cut and mounted in a 2.5-ml muscle chamber. They were perfused with Tyrode''s solution and oxygenated continuously. After equilibration for 1 h, perfusion was stopped and one strip from the lower esophageal sphincter region was incubated in solution that contained 12-25 parts of VIP antiserum per 1000 of Tyrode''s solution, while a 2nd strip was incubated in a solution of normal rabbit serum at the same concentration. A 3rd strip was maintained in Tyrode''s solution for the duration of the experiment. After a 1-h incubation, the strips were stimulated with 6-s square wave trains of 0.1-, 0.2-, 0.4-, and 0.8-ms pulses at 1, 2 and 5 Hz. These stimulation parameters produced LES relaxation that was completely blocked by tetrodotoxin but not by atropine or phentolamine. The strips incubated in Tyrode''s solution or in normal serum relaxed reliably and consistently at all levels of stimulation. In the antiserum-treated strips, LES relaxation in response to all stimuli was significantly inhibited. Strips treated with normal serum were relaxed in a dose-dependent fashion by 10-7 and 10-6 M VIP, whereas the antiserum inhibited the relaxation induced by 10-7 M, but not by 10-6 M, VIP. Stimulation with 2 successive 15-min trains of electrical pulses (2 ms, 5 Hz) separated by 30 min of rest released increasing amounts of VIP into the bathing solution. VIP released during the 2nd train of electrical stimulation was significantly (P < 0.05) greater than in control conditions. In the cat LES, VIP antiserum inhibits the relaxation induced by exogenous VIP or by electric stimulation of nonadrenergic, noncholinergic inhibitory nerves at a level that causes the release of VIP. VIP may be an inhibitory neurotransmitter responsible for LES relaxation.