Neural release of vasoactive intestinal peptide from the gut.
The release of vasoactive intestinal peptide (VIP) from the canine gut and its possible neural origin were studied using two agents, oxytocin and neostigmine, known to increase peripheral levels of VIP. Oxytocin and neostigmine increased the portal concentrations of VIP by threefold and sevenfold, respectively. A considerable portal/femoral vein gradient ranging from twofold in the basal state to sevenfold during stimulation with neostigmine indicated that the gut was the main source of circulating VIP. The contribution of the brain was minor, and that of the uterus was undetectable. Release of VIP occurred from the entire gut: After enterectomy, the residual gut (stomach, pancreas, and proximal duodenum) released spontaneously a large amount of VIP which masked the effect of oxytocin. Tetrodotoxin and hexamethonium, but not atropine, inhibited oxytocin-stimulted release of VIP by 80% and 60% respectively. This prompted the conclusion that the release of VIP was predominantly neurally mediated and that the chain of transmission involved a preganglionic cholinergic pathway. Hexamethonium strongly inhibited neostigmine-stimulated release of VIP. Atropine was even more potent in that it abolished the effect of neostigmine. The effect of atropine was attributed to a blockade of ganglionic muscarinic receptors, which are preferentially activated by cholinesterase inhibitors like neostigmine. The results of this study and those derived from electrical stimulation of the vagus nerve are consistent with the hypothesis that circulating VIP is released from intrinsic neurons of the gut under preganglionic cholinergic control.
D000818:Animals; D001339:Autonomic Fibers, Preganglionic / Q000502:physiology*; D003864:Depression, Chemical; D004285:Dogs; D005260:Female; D005768:Gastrointestinal Hormones / Q000378:metabolism*; D006584:Hexamethonium Compounds / Q000494:pharmacology; D006728:Hormones / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000294:innervation*; D009388:Neostigmine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D010121:Oxytocin / Q000037:antagonists & inhibitors / Q000494:pharmacology; D011950:Receptors, Cholinergic / Q000502:physiology*; D011976:Receptors, Muscarinic / Q000502:physiology*; D013268:Stimulation, Chemical; D013779:Tetrodotoxin / Q000494:pharmacology; D014660:Vasoactive Intestinal Peptide / Q000378:metabolism*
D005768:Gastrointestinal Hormones; D006584:Hexamethonium Compounds; D006728:Hormones; D011950:Receptors, Cholinergic; D011976:Receptors, Muscarinic; D014660:Vasoactive Intestinal Peptide; D009388:Neostigmine; D013779:Tetrodotoxin; D010121:Oxytocin