Vasoactive intestinal peptide as a neural mediator of gastric relaxation

Abstract

Two main candidates, ATP and vasoactive intestinal peptide (VIP), were proposed as inhibitory transmitters at neuromuscular junctions in the gut. A photoaffinity analog at ATP, 3''-O-(4-benzoyl)benzoyl ATP or BzATP, that binds covalently to ATP receptors and inactivates them in the presence of light and a specific high-affinity VIP antiserum were used in order to examine the contributions of ATP and VIP to neurally induced relaxation in circular smooth muscle of the gastric fundus of the guinea pig. VIP and ATP caused dose-dependent relaxation; the effect of ATP was equal to that of its stable isostere, .alpha.,.beta.-methylene ATP, and was resistant to degradation by adenosine deaminase, indicating interaction of ATP with purinergic P2-receptors. Relaxation induced by VIP was selectively inhibited by VIP antiserum (final dilution 1:120), while that induced by ATP was selectively inhibited by photoactivated BzATP. Relaxation induced by electrical field (i.e., neural) stimulation was inhibited by VIP antiserum only; photoactivated BzATP had no effect. Inhibition of neurally induced relaxation ranged from 86% (P < 0.01) at the lowest frequencies to 34% (P < 0.01) at the highest frequencies. Maximal field stimulation caused an 11-fold increase in VIP release from intramural neurons. VIP is strongly favored as the neural mediator of gastric relaxation.