원저 : Vasoactive Intestinal Polypeptide 의 뇌실내 투여가 위산분비 및 위궤양 발생에 미치는 영향

Vasoactive intestinal polypeptide (VIP) is a peptide composed of 28 amino acids that was first isolated from the porcine duodenum. Although VIP was primarily considered to be a gut hormone, it has been shown to occur in central and peripheral neuron. At present, it is accepted that VIP acts as a neurotransmitter or a neuromodulator both in central and peripheral nervous system. Recently immunohistochemical studies have shown that the vagus nerve contains not only acetylcholine but also other neurotransmitters including VIP. These findings suggest that the central control of acid secretion is considerably complex and raised the possibility that multiple neurotransmitters may affect the secretory function of the gastric parietal cell. In this context, VIP might be involved in the central regulation of acid secretion, which is yet to be investigated. In present study, the effects of intracerebroventricular (icv) administration of VIP on the gastric secretion as well as its mechanism and stress ulceration were investigated in Sprague-Dawley rats of either sex weighing about 200 g. The results are summarized as follows. 1. ICV injection of VIP increased secretion of gastric acid and pepsin in a dose-dependent manner upto 1 pg. However, higher doses (3-10 pg) fail to stimulate further the gastric secretion. 2. The secretion of gastric acid and pepsin induced by icv VIP was abolished by bilateral vagotomy as well as by atropine or pirenzepine. 3. The effect of icv VIP on gastric secretion was prevented by hemicholinium or desipramine. Metyrosine delayed the stimulatory response of gastric function induced by icv VIP. 4. Cimetidine inhibited the basa] and icv VIP-induced gastric secretion. 5. Stress-induced ulceration in pylorus-ligated restraint rats was aggravated by icv injection of VIP. From the above results, it is demonstrated that intracerebroventricular VIP stimulates gastric acid and pepsin secretion, and aggravates stress-induced ulceration, and is suggested that these effects are mediated by cholinergic mechanism via central vagal activation.