EFFECT OF WEBERINE AND ITS CONGENERS ON VASCULAR SMOOTH MUSCLE CONTRACTILITY

韦伯林及其同系物对血管平滑肌收缩力的影响

• 批准号: 6239947
• 负责人: MOHAMMED A MALEQUE
• 金额: $ 9.68万
• 依托单位: MEHARRY MEDICAL COLLEGE
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-08-01 至 1998-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6239947
• 关键词: adrenergic receptor; alkaloids; brain cell; calcium flux; chemical structure function; drug adverse effect; drug screening /evaluation; hypertension; inhibitor /antagonist; inositol phosphates; laboratory rabbit; laboratory rat; muscle contraction; phenylalkylamine; phenylethylamines; plant extracts; psychotomimetic drug; receptor binding; serotonin receptor; vascular smooth muscle; vasoconstriction

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.

本课题的目的是研究小檗碱的作用 及其同系物对血管平滑肌收缩性的影响。韦贝林是 一种仙人掌属植物生物碱，结构上与拟精神病药有关 试剂是环取代的苯基烷基胺，或 吲哚烷基胺。据报道，拟精神病药物 例如美斯卡灵和麦角酰二乙胺（LSD）， 高血压 然而，这些药剂对 高血压不明确。Mescaline和LSD通过肾上腺素能和 与Ca 2-内流相关的钙离子能受体， 磷脂酰肌醇血管上发现的这些受体的激活 平滑肌引起血管收缩。因此，我们假设， 小檗碱及其同类物产生主动脉平滑肌收缩力 通过与肾上腺素能和肾上腺素能受体相互作用。此外，委员会认为， 由于肾上腺素能和肾上腺素能受体与Ca 2-内流有关， 和磷酸肌醇介导的血管收缩，我们打算研究 小檗碱及其同类物和美斯卡灵对家兔的作用 主动脉和大鼠脑组织。这些研究将使我们能够 确定：l.这些化合物对血管平滑肌的效力 收缩性，2.这些化合物的效力和选择性 使用受体特异性拮抗剂的α 1和5-HT 2受体，3. 的 这些化合物对细胞外或细胞内钙离子的作用 收缩，4。这些化合物亲和力和选择性 对于α 1和5-HT 2受体亚型，使用受体特异性 放射性配体结合测定，和5.这些化合物对 肌醇三磷酸水平。我们希望由此获得的数据 项目将有助于提供知识，以更好地了解 精神分裂症诱发的高血压的机制，从而帮助 开发可能预防或 逆转这些拟精神病药物的不良作用。