Bhargava H N, Gulati A
Department of Pharmacodynamics, Health Sciences Center, University of Illinois, Chicago 60612.
Peptides. 1988 Jul-Aug;9(4):771-5. doi: 10.1016/0196-9781(88)90120-9.
The effect of naturally occurring cannabinoids, delta 9-tetrahydrocannabinol (THC), cannabinol (CBN) and cannabidiol (CBD), on the brain receptors for thyrotropin releasing hormone (TRH) was investigated. TRH receptors were labeled with 3H-(3-MeHis2)TRH (3H-MeTRH). 3H-MeTRH bound specifically to rat brain membranes at a single high affinity site with a Bmax value of 49.2 +/- 0.96 fmol per mg protein and a Kd value of 3.83 +/- 0.12 nM. The binding of 3H-MeTRH to whole brain membranes was inhibited when rats were injected intraperitoneally with 3 to 30 mg/kg of THC. The extent of inhibition in the binding at 10 and 30 mg/kg was similar. THC (10 mg/kg) significantly inhibited the binding of 3H-MeTRH to amygdala membranes but did not affect the binding to membranes prepared from hippocampus, septum, cortex, striatum and the rest of the brain. THC, CBN and CBD in doses of 3 to 30 mg/kg did not affect the binding of 3H-MeTRH to hypothalamic membranes. All the three cannabinoids at 30 mg/kg inhibited the binding of 3H-MeTRH to amygdala membranes. The inhibition in the binding of 3H-MeTRH by the cannabinoids was due to changes in the Kd values but the Bmax values remained unchanged. It is concluded that both psychotomimetic and nonpsychotomimetic cannabinoids inhibit the binding of 3H-MeTR to amygdala membranes selectively, which is accomplished by decreases in the affinity of the ligand to receptors, and the amygdala may be an important brain area in some of the actions of cannabinoids.
研究了天然存在的大麻素，即δ9-四氢大麻酚（THC）、大麻酚（CBN）和大麻二酚（CBD）对促甲状腺激素释放激素（TRH）脑受体的影响。用3H-（3-甲基组氨酸2）TRH（3H-MeTRH）标记TRH受体。3H-MeTRH以单一高亲和力位点特异性结合大鼠脑膜，每毫克蛋白质的Bmax值为49.2±0.96 fmol，Kd值为3.83±0.12 nM。当给大鼠腹腔注射3至30 mg/kg的THC时，3H-MeTRH与全脑膜的结合受到抑制。10和30 mg/kg时结合抑制程度相似。THC（10 mg/kg）显著抑制3H-MeTRH与杏仁核膜的结合，但不影响与海马、隔区、皮质、纹状体及脑其他部位制备的膜的结合。3至30 mg/kg剂量的THC、CBN和CBD不影响3H-MeTRH与下丘脑膜的结合。所有三种大麻素在30 mg/kg时均抑制3H-MeTRH与杏仁核膜的结合。大麻素对3H-MeTRH结合的抑制是由于Kd值的变化，但Bmax值保持不变。结论是拟精神病性和非拟精神病性大麻素均选择性抑制3H-MeTR与杏仁核膜的结合，这是通过配体与受体亲和力的降低实现的，杏仁核可能是大麻素某些作用中的一个重要脑区。
