EFFECT OF WEBERINE AND ITS CONGENERS ON VASCULAR SMOOTH MUSCLE CONTRACTILITY

本项目的目的是研究黄连素的作用。 及其同系物对血管平滑肌收缩性能的影响。韦伯林是 一种仙人掌植物生物碱，在结构上与拟精神病药有关 环取代苯基烷基胺或 吲哚乙基胺。据报道，拟精神分裂症药物 例如美斯卡林和麦角酸二乙胺(LSD)会导致严重 高血压。然而，这些药物的作用机制是 高血压尚不清楚。美斯卡林和LSD通过肾上腺素能和 5-羟色胺能受体与钙内流和 磷酸肌醇。血管上发现的这些受体的激活 平滑的肌肉会引起血管收缩。因此，我们假设 Weberine及其同系物产生主动脉平滑肌收缩功能 通过与肾上腺素能和5-羟色胺能受体相互作用。此外， 由于肾上腺素能和5-羟色胺能受体与钙内流有关 和磷酸肌醇介导的血管收缩，我们打算研究 黄连素和美斯卡林的同系物黄连素对兔的影响 主动脉和大鼠脑组织。这些研究将使我们能够 测定：L.这些化合物对血管平滑肌的效力 收缩性能，2.这些化合物的效力和选择性 使用受体特异性拮抗剂的α1和5-HT2受体，3. 这些化合物对细胞外或细胞内钙离子的影响(S) 诱导收缩，4.这些化合物的亲和力和选择性 对于α1和5-HT2受体亚型，使用受体特异性 放射性配基结合分析，以及5.这些化合物的作用(S)。 三磷酸肌醇水平。我们希望从这一过程中获得的数据 项目将有助于提供知识，以便更好地了解 拟精神分裂症诱发高血压的机制及由此而有助于 潜在的拮抗者(S)的发展，可以防止或 逆转这些拟精神分裂药剂的不良影响。

The objective of this project is to investigate the effect of weberine and its congeners on vascular smooth muscle contractility. Weberine is a cactus plant alkaloid that is structurally related to psychotomimetic agents which are ring substituted phenylalkylamines or indolealkylamines. It has been reported that psychotomimetic agents such as mescaline and lysergic acid diethylamide (LSD) cause severe hypertension. However, the mechanism of action of these agents on hypertension is not clear. Mescaline and LSD act through adrenergic and serotonergic receptors which are linked to Ca2- influx and phosphotidylinositol. Activation of these receptors found on vascular smooth muscle causes vasoconstriction. Thus, we hypothesize that weberine and its congeners produce aortic smooth muscle contractility by interacting with adrenergic and serotonergic receptors. Furthermore, since adrenergic and serotonergic receptors are linked to Ca2- influx and phosphoinositol mediated vasoconstriction, we intend to study the effect of weberine, the congeners of weberine and mescaline on rabbit aortic and rat brain tissues. These studies will enable us to determine: l. the potency of these compounds on vascular smooth muscle contractility, 2. the potency and selectivity of these compounds on alpha1 and 5-HT2 receptors using receptor specific antagonists, 3. the effect(s) of these compounds on extracellular or intracellular calcium- induced contraction, 4. the affinity and selectivity of these compounds for alpha1 and 5-HT2 receptor subtypes using receptor specific radioligand binding assays, and 5. the effect(s) of these compounds on inositol triphosphate levels. We hope that the data obtained from this project will help to provide knowledge to better understand the mechanism of psychotomimetic-induced hypertension and thereby aid in the development of potential antagonist(s) that could prevent or reverse the undesirable effects of these psychotomimetic agents.