Hinson J P, Puddefoot J R, Kapas S
Molecular and Cellular Biology Section, Division of Biomedical Sciences, St Bartholomew's and The Royal London School of Medicine and Dentistry, Queen Mary and Westfield College, Mile End Road, London E1 4NS, UK.
J Endocrinol. 1999 Apr;161(1):51-7. doi: 10.1677/joe.0.1610051.
Previous studies, by this group and others, have shown that vasoactive intestinal peptide (VIP) stimulates aldosterone secretion, and that the actions of VIP on aldosterone secretion by the rat adrenal cortex are blocked by beta adrenergic antagonists, suggesting that VIP may act by the local release of catecholamines. The present studies were designed to test this hypothesis further, by measuring catecholamine release by adrenal capsular tissue in response to VIP stimulation. Using intact capsular tissue it was found that VIP caused a dose-dependent increase in aldosterone secretion, with a concomitant increase in both adrenaline and noradrenaline release. The effects of VIP on aldosterone secretion were inhibited by atenolol, a beta1 adrenergic antagonist, but not by ICI-118,551, a beta2 adrenergic antagonist. Binding studies were carried out to investigate VIP receptors. It was found that adrenal zona glomerulosa tissue from control rats contained specific VIP binding sites (Bmax 853+/-101 fmol/mg protein; Kd 2.26+/-0.45 nmol/l). VIP binding was not displaced by ACTH, angiotensin II or by either of the beta adrenergic antagonists. The response to VIP in adrenals obtained from rats fed a low sodium diet was also investigated. Previous studies have found that adrenals from animals on a low sodium diet exhibit increased responsiveness to VIP. Specific VIP binding sites were identified, although the concentration or affinity of binding sites in the low sodium group was not significantly different from the controls. In the low sodium group VIP was found to increase catecholamine release to the same extent as in the control group, however, in contrast to the control group, the adrenal response to VIP was not altered by adrenergic antagonists in the low sodium group. These data provide strong support for the hypothesis that VIP acts by the local release of catecholamines in adrenal zona glomerulosa tissue in normal animals. It does not appear that VIP acts through the same mechanism in animals maintained on a low sodium diet. The mechanism by which VIP stimulates aldosterone in this group remains to be determined.
该研究团队以及其他团队之前的研究表明，血管活性肠肽（VIP）可刺激醛固酮分泌，并且β肾上腺素能拮抗剂可阻断VIP对大鼠肾上腺皮质醛固酮分泌的作用，这表明VIP可能通过局部释放儿茶酚胺发挥作用。本研究旨在通过测量肾上腺被膜组织对VIP刺激的儿茶酚胺释放量，进一步验证这一假设。使用完整的被膜组织发现，VIP可引起醛固酮分泌呈剂量依赖性增加，同时肾上腺素和去甲肾上腺素释放量也随之增加。β1肾上腺素能拮抗剂阿替洛尔可抑制VIP对醛固酮分泌的作用，但β2肾上腺素能拮抗剂ICI-118,551则无此作用。进行了结合研究以探究VIP受体。发现对照大鼠的肾上腺球状带组织含有特异性VIP结合位点（Bmax为853±101 fmol/mg蛋白质；Kd为2.26±0.45 nmol/l）。促肾上腺皮质激素（ACTH）、血管紧张素II或任何一种β肾上腺素能拮抗剂均不能取代VIP的结合。还研究了低钠饮食喂养大鼠的肾上腺对VIP的反应。之前的研究发现，低钠饮食动物的肾上腺对VIP的反应性增强。尽管低钠组结合位点的浓度或亲和力与对照组无显著差异，但仍鉴定出了特异性VIP结合位点。在低钠组中，发现VIP增加儿茶酚胺释放的程度与对照组相同，然而，与对照组不同的是，低钠组中肾上腺素能拮抗剂并未改变肾上腺对VIP的反应。这些数据为VIP通过正常动物肾上腺球状带组织中局部释放儿茶酚胺发挥作用这一假设提供了有力支持。在低钠饮食喂养的动物中，VIP似乎并非通过相同机制发挥作用。该组中VIP刺激醛固酮分泌的机制仍有待确定。
