Sapena R, Morin D, Zini R, Morin C, Tillement J P
Département de Pharmacologie, Faculté de Médecine de Paris XII, Créteil, France.
Eur J Pharmacol. 1996 Apr 4;300(1-2):159-62. doi: 10.1016/0014-2999(96)00060-x.
Eight days' desipramine administration (16 mg/kg per day i.p.) to rats resulted in a significant decrease in the density of beta-adrenoceptors in neuronal and astroglial cells from rat forebrain and cerebellum without modification of their corresponding affinity. beta-Adrenoceptor subtypes, beta 1 and beta 2, which coexist in neurons and astrocytes, are differently distributed in the brain and differently modified by desipramine administration which down-regulates beta 1-adrenoceptor in forebrain neurons and astrocytes and beta 2-adrenoceptor in cerebellum neurons. This down-regulation affects the predominant subtype, beta 1 or beta 2, of the relevant structure. Astroglial and neuronal beta-adrenoceptors are differently coupled to G-proteins. Only neuronal cells contain the high-affinity conformational state of the beta-adrenoceptors which is sensitive to GTP. The percentage of neuronal receptors in the high-affinity state differs according to brain area. Desipramine treatment decreases the neuronal density of both cerebellar high- and low-affinity sites and only the forebrain high-affinity site. The desipramine effects are thus subtype-dependent and differ between the two brain areas selected.
给大鼠连续八天腹腔注射地昔帕明（每天16毫克/千克），导致大鼠前脑和小脑中神经元和星形胶质细胞的β-肾上腺素能受体密度显著降低，而其相应亲和力未发生改变。共存于神经元和星形胶质细胞中的β-肾上腺素能受体亚型β1和β2，在脑中分布不同，且地昔帕明给药对其修饰不同，地昔帕明下调前脑神经元和星形胶质细胞中的β1-肾上腺素能受体以及小脑神经元中的β2-肾上腺素能受体。这种下调影响相关结构中占主导地位的亚型β1或β2。星形胶质细胞和神经元的β-肾上腺素能受体与G蛋白的偶联方式不同。只有神经元细胞含有对GTP敏感的β-肾上腺素能受体的高亲和力构象状态。处于高亲和力状态的神经元受体百分比因脑区而异。地昔帕明治疗降低了小脑高亲和力和低亲和力位点以及仅前脑高亲和力位点的神经元密度。因此，地昔帕明的作用是亚型依赖性的，并且在所选择的两个脑区之间存在差异。
