CANNABINOID EFFECTS ON MEMBRANES AND THEIR CONSTITUENTS

三角洲-9四氢大麻酚(THC)，主要的行为活性物质 大麻中的一种成分可以影响一种 各种与膜相关的酶和受体。THC还可以有一个 流态化或无序对人工脂双层膜的影响 (脂质体)和突触质膜。基于对此的观察 类型，已经提出了一种假设，即THC和 其他大麻素的部分原因是这些化合物对 生物膜或膜内特定区域的排序。 这项建议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蛋白质流动性的影响 并探索这些变化与 这些化合物对肾上腺素能受体及其相关受体的影响 腺苷环化酶和Na+K+-ATPase。将制备质膜 从大鼠的大脑、心脏和肝脏中提取。两种大麻素对人体的影响 有3人有类似大麻的行为活动，有很少或根本没有 大麻样行为对膜有序性(流动性)的影响 用荧光偏振技术测定。类似的研究 将使用具有各种脂类的人工脂双层来进行 组成和初始流度。同样的大麻素的影响 β-肾上腺素能受体及其偶联的腺苷环化酶等 还将在大脑、心脏和肝脏中检测Na+-K+-ATPase。阿雷尼乌斯 还将确定酶活性的曲线图。因为这些研究 都是执行的，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 受体将被分析为精神活性(类THC)和 非精神活性大麻素。希望有一个一致的模式 变化将出现，这将增加我们对分子的洞察 大麻及其成分的行为。

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.