CANNABINOID EFFECTS ON MEMBRANES AND THEIR CONSTITUENTS

大麻素对膜及其成分的影响

• 批准号: 3208329
• 负责人: ALAN S BLOOM
• 金额: $ 11.92万
• 依托单位: MEDICAL COLLEGE OF WISCONSIN
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-07-01 至 1988-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3208329
• 关键词: adenosinetriphosphatase; adenylate cyclase; cannabinoids; chemical structure function; drug adverse effect; drug metabolism; fluorescence polarization; fluorescence spectrometry; fluorescent dye /probe; liposomes; membrane lipids; membrane structure; neuropharmacology; phospholipids; saturated fatty acids; unsaturated fatty acids

Delta-9 Tetrahydrocannabinol (THC), the principal behaviorally active constituent in marijuana can affect the activity or functioning of a variety of membrane-associated enzymes and receptors. THC can also have a fluidizing or disordering affect on artificial lipid bilayer membranes (liposomes) and synaptic plasma membranes. Based on observations of this type, a hypothesis has been proposed stating that the effects of THC and other cannabinoids are due in part to the effects of these compounds on the ordering of biological membranes or specific regions within the membrane. The experiments in this proposal should enable us to describe and quantify the effects of several cannabinoids on the fluidity of biological and artificial membranes and explore the relationship of these changes to effects of these same compounds on adrenergic receptors and their associate adenylate cyclase and on Na+ K+-ATPase. Plasma membranes will be prepared from rat brain, heart, and liver. The effects of two cannabinoids with marijuana-like behavioral activity and three with little or no marijuana-like behavioral activity on membrane ordering (fluidity) will be determined using fluorescence polarization techniques. Similar studies will be performed using artificial lipid bilayers with a variety of lipid compositions and initial fluidities. The effects of the same cannabinoids on Beta-adrenergic receptors and their coupled adenylate cyclase and on Na+-K+-ATPase will also be examined in brain, heart, and liver. Arrhenius plots for the enzyme activities will also be determined. As these studies are performed, the developing pattern of relationships between membrane type (initial fluidity), fluidity changes, and changes in enzymes and receptors will be analyzed for both the psychoactive (THC-like) and non-psychoactive cannabinoids. It is hoped that a consistent pattern of changes will emerge that will increase our insight into the molecular actions of marijuana and its constituents.

Delta-9四氢大麻酚（THC），主要的行为活性 大麻中的一种成分可以影响一种 多种膜相关酶和受体。 THC也可以有一个 对人工脂双层膜的流化或无序化影响 （脂质体）和突触质膜。 根据对这一现象的观察， 类型，提出了一个假设，指出THC和 其他大麻素部分是由于这些化合物对 生物膜或膜内特定区域的排序。 这项提案中的实验应该使我们能够描述和量化 几种大麻素对生物和 人工膜，并探讨这些变化与 这些化合物对肾上腺素能受体及其相关受体的作用 腺苷酸环化酶和Na ~+-K ~+-ATP酶。 将制备质膜 老鼠的大脑心脏和肝脏 两种大麻素的作用 大麻样行为活动和三个很少或没有 大麻样的行为活动对膜秩序（流动性）将是 使用荧光偏振技术测定。 类似研究 将使用具有多种脂质的人工脂质双层进行 组成和初始流动性。 同样的大麻素 对β-肾上腺素能受体及其偶联腺苷酸环化酶和对 还将检查脑、心脏和肝脏中的Na+-K+-ATP酶。 Arrhenius 还将确定酶活性的曲线。 因为这些研究 膜之间关系的发展模式 类型（初始流动性）、流动性变化以及酶和 受体将分析精神活性（THC样）和 非精神活性大麻素 人们希望， 这些变化将增加我们对分子的了解， 大麻及其成分的作用。