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人体内的血管活性肠肽:药代动力学、代谢及循环效应

Vasoactive intestinal peptide in man: pharmacokinetics, metabolic and circulatory effects.

作者信息

Domschke S, Domschke W, Bloom S R, Mitznegg P, Mitchell S J, Lux G, Strunz U

出版信息

Gut. 1978 Nov;19(11):1049-53. doi: 10.1136/gut.19.11.1049.

Abstract

Graded doses of 0.6, 1.3, and 3.3 pmol/kg/min of vasoactive intestinal peptide (VIP) were intravenously infused over 30 minute periods in four healthy volunteers and plasma VIP levels were measured by radioimmunoassay. Even with the smallest dose of VIP, plasma concentrations rose markedly above normal values. Infusion of higher VIP doses resulted in mean plateau levels of circulating VIP which were in the range of VIP values found in the Verner-Morrison syndrome. After cessation of the VIP infusions, plasma VIP levels fell strikingly by first order kinetics with an average disappearance half-time of one minute. The apparent metabolic clearance rate was about 9 ml/kg/min and the apparent volume of distribution for VIP was approximately 14 ml/kg. During infusion of the highest VIP dose, previously shown to induce one-fifth maximum pancreatic juice secretion, plasma concentrations of glucose, free fatty acids, and calcium were slightly but significantly raised, the pulse rate and the amplitude of blood pressure were increased, and cutaneous flushing occurred. The spectrum of effects accords well with some abnormalities seen in the Verner-Morrison syndrome. The present data, however, do not support a role for VIP as a circulating hormone, at least under physiological conditions.

摘要

在4名健康志愿者中,在30分钟内静脉输注0.6、1.3和3.3 pmol/kg/min的不同剂量血管活性肠肽(VIP),并通过放射免疫分析法测量血浆VIP水平。即使使用最小剂量的VIP,血浆浓度也明显高于正常值。输注更高剂量的VIP导致循环中VIP的平均平台水平,处于韦纳-莫里森综合征中发现的VIP值范围内。停止输注VIP后,血浆VIP水平以一级动力学显著下降,平均消失半衰期为1分钟。表观代谢清除率约为9 ml/kg/min,VIP的表观分布容积约为14 ml/kg。在输注先前已证明可诱导五分之一最大胰液分泌的最高VIP剂量期间,血浆葡萄糖、游离脂肪酸和钙的浓度略有但显著升高,脉搏率和血压幅度增加,并且出现皮肤潮红。这些效应谱与韦纳-莫里森综合征中所见的一些异常情况非常吻合。然而,目前的数据不支持VIP作为循环激素的作用,至少在生理条件下如此。

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