NHLBI MINORITY SCHOOL FACULTY DEVELOPMENT AWARD

本项目的目的是研究西黄碱和黄连素的作用。 其同系物对血管平滑肌的收缩能力。韦伯林是一位 仙人掌植物生物碱，在结构上与拟精神分裂症有关 环取代苯基烷基胺或吲哚烷基胺的试剂。 据报道，梅斯卡林和美斯卡林等拟精神分裂症药物 麦角酸二乙胺(LSD)会导致严重的高血压。然而， 这些药物对高血压的作用机制尚不清楚。 美斯卡林和LSD通过肾上腺素能和5-羟色胺能受体发挥作用 与钙离子内流和磷脂酰肌醇有关。激活这些 血管平滑肌上发现的受体会引起血管收缩。因此， 我们假设Weberine和它的同系物产生主动脉平滑肌 通过与肾上腺素能和5-羟色胺能受体相互作用的收缩能力。 此外，由于肾上腺素能和5-羟色胺能受体与钙离子有关 内流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确定： 1.这些化合物对血管平滑肌收缩的效力， 2.这些化合物对α_1和5-HT2的活性和选择性。 使用受体特异性拮抗剂的受体，3.它们的作用(S) 对细胞外或细胞内钙引起的收缩的化合物，4. 这些化合物对α-1和5-HT2的亲和力和选择性 使用受体特异性放射配基结合分析的受体亚型，以及 5.这些化合物对三磷酸肌醇水平的影响(S)。我们 希望从这个项目中获得的数据将有助于提供 更好地理解拟精神分裂症诱导机制的知识 高血压，从而有助于潜在拮抗剂的发展(S) 可以防止或扭转这些不良影响 精神分裂药剂。

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: 1. 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.