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1. The release of vasoactive intestinal polypeptide from the gastrointestinal tract in response to stimulation of the vagus nerves, the splanchnic nerves and to intra-arterial infusion of acetylcholine (ACh) was examined in pigs. 2. Stimulation of the vagus nerves caused an abrupt increase in the release of vasoactive intestinal polypeptide. The amount of the peptide released depended on the frequency at which the nerves were stimulated. Maximum release was obtained at 8 Hz. 3. Atropine and beta-adrenergic blocking agents failed to diminish the vagally induced release of vasoactive intestinal polypeptide, while the response was completely blocked by hexamethonium and increased after alpha-adrenergic blockade and after splanchnicotomy. 4. Intra-arterial infusion of ACh closely imitated the response to vagal stimulation, but the release of vasoactive intestinal polypeptide induced by ACh was abolished by atropine. 5. Stimulation of the splanchnic nerves caused a decrease in the release of vasoactive intestinal polypeptide, an action which was annulled by alpha-adrenergic blockade, but still present after the adrenal glands were isolated from the circulation. The inhibitory effect of splanchnic stimulation significantly diminished the vagally induced release of vasoactive intestinal polypeptide. 6. The results demonstrate a dual innervation with opposing effects on the neurones containing vasoactive intestinal polypeptides. The possible physiologic implication of this finding is discussed.

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