Studies of the role of membrane lipid order in the effects of delta 9-tetrahydrocannabinol on adenylate cyclase activation in heart.
Studies of the role of membrane lipid order in the effects of delta 9-tetrahydrocannabinol on adenylate cyclase activation in heart.
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发表时间：
1990-03
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通讯作者：
C. Hillard;J. J. Pounds-J.;D. Boyer;A. Bloom
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作者：
C. Hillard;J. J. Pounds-J.;D. Boyer;A. Bloom
本报告中的研究旨在研究δ 9-四氢大麻酚（δ 9-THC）对心肌膜腺苷酸环化酶活性的影响，并确定膜脂质顺序变化在这些影响中的作用。δ 9-THC及其精神活性代谢物11-OH-δ 9-THC增加了大鼠心室膜中异丙肾上腺素（ISO）对腺苷酸环化酶的刺激。大麻二酚、大麻酚和（+）-δ 9-THC都没有作用，表明δ 9-THC的这种作用是立体选择性的，并且对具有精神活性效力的大麻素是特异性的。Δ 9-THC也增加胰高血糖素对腺苷酸环化酶的刺激。ISO和胰高血糖素刺激的腺苷酸环化酶的增强是由于这些激动剂的Vmax增加而Kact无显著变化。Δ 9-THC不影响基础腺苷酸环化酶活性或由毛喉素、鸟嘌呤核苷酸或氟离子引起的酶活化。那些增加ISO刺激的腺苷酸环化酶活性的大麻素也降低了Arrhenius图的断裂温度;证据表明δ 9-THC的作用涉及膜磷脂顺序的变化。用荧光偏振法研究了大麻素对心肌膜磷脂有序性的影响。δ 9-THC和11-OH-δ 9-THC单独降低了二苯基己三烯温度曲线的断裂温度，即，降低了脂相分离的温度。Δ 9-THC的这种作用是立体选择性的。（250字处删节）
The studies in this report were carried out to investigate the effects of delta 9-tetrahydrocannabinol (delta 9-THC) on cardiac membrane adenylate cyclase activity and to determine the role of changes in membrane lipid order in these effects. delta 9-THC and its psychoactive metabolite, 11-OH-delta 9-THC, increased isoproterenol (ISO) stimulation of adenylate cyclase in rat cardiac ventricular membranes. Cannabidiol, cannabinol and (+)-delta 9-THC were all without effect, indicating that this effect of delta 9-THC is stereoselective and specific for cannabinoids with psychoactive potency. delta 9-THC also increased glucagon stimulation of adenylate cyclase. The enhancement of both ISO and glucagon-stimulated adenylate cyclase was due to an increase in the Vmax of these agonists with no significant change in Kact. delta 9-THC did not affect basal adenylate cyclase activity or the activation of the enzyme by forskolin, guanine nucleotides or fluoride ion. Those cannabinoids which increased ISO-stimulated adenylate cyclase activity also decreased the break temperature of the Arrhenius plot; evidence that the effects of delta 9-THC involve changes in membrane phospholipid order. The effects of the cannabinoids on cardiac membrane phospholipid order were investigated directly using diphenylhexatriene fluorescence polarization. delta 9-THC and 11-OH-delta 9-THC alone decreased the break temperature of the diphenylhexatriene temperature profile, i.e., decreased the temperature of the lipid phase separation. This effect of delta 9-THC was stereoselective.(ABSTRACT TRUNCATED AT 250 WORDS)