Chaudhry A, Lahners K N, Granneman J G
Department of Psychiatry, Wayne State University School of Medicine, Detroit, Michigan.
J Pharmacol Exp Ther. 1992 May;261(2):633-7.
The stimulation of adenylyl cyclase by catecholamines in neonatal brown adipose tissue (BAT) is markedly biphasic, suggesting the existence of receptors that have both high and low affinities for catecholamines. The identities of these receptors were examined by comparing responses in neonatal BAT membranes to those of Chinese hamster ovary cells which had been transfected to express the cloned rat beta 1 and beta 3 receptors. The results from these experiments indicate that high-affinity stimulation of adenylyl cyclase by catecholamines in BAT is mediated by beta 1 receptors, as evidenced by the potencies of norepinephrine and isoproterenol at this receptor and the potent blockade of the receptor by alprenolol. The low-affinity catecholamine receptor appears to be the beta 3 receptor, as indicated by the low potency of catecholamine agonists and the inability of low concentrations of alprenolol to block this activity. Furthermore, this receptor, like the cloned rat beta 3 receptor, was antagonized by (-)-4-(3-t-butylamino-2-hydroxypropoxy)benzimidazol-2-one (CGP 12177) and was stimulated by (R',R')-4-(2-[(2[(3-chlorophenyl)-2- hydroxyethyl]amino)propyl]phenyl)phenoxyacetic acid (BRL 37344). These results indicate that both beta 1 and beta 3 receptors couple to adenylyl cyclase in BAT and that activation of adenylyl cyclase in neonatal BAT is mediated primarily by beta 3 receptors. Beta 3 receptors were also clearly detected in weanling BAT with the beta 3-selective agonist BRL 37344. However, when catecholamines were used to stimulate activity, the activation of adenylyl cyclase by beta 1 receptors, which occurred at low concentrations of catecholamines, obscured the activation of adenylyl cyclase by beta 3 receptors, which occurred only at high concentrations.
儿茶酚胺对新生动物棕色脂肪组织（BAT）中腺苷酸环化酶的刺激作用具有明显的双相性，这表明存在对儿茶酚胺具有高亲和力和低亲和力的受体。通过比较新生动物BAT膜与转染后表达克隆大鼠β1和β3受体的中国仓鼠卵巢细胞的反应，来研究这些受体的特性。这些实验结果表明，BAT中儿茶酚胺对腺苷酸环化酶的高亲和力刺激作用是由β1受体介导的，去甲肾上腺素和异丙肾上腺素对该受体的效力以及阿普洛尔对该受体的有效阻断证明了这一点。低亲和力的儿茶酚胺受体似乎是β3受体，这由儿茶酚胺激动剂的低效价以及低浓度阿普洛尔无法阻断该活性表明。此外，该受体与克隆的大鼠β3受体一样，被（-）-4-（3-叔丁基氨基-2-羟基丙氧基）苯并咪唑-2-酮（CGP 12177）拮抗，并被（R'，R'）-4-（2-[(2[(3-氯苯基)-2-羟乙基]氨基)丙基]苯基）苯氧基乙酸（BRL 37344）刺激。这些结果表明，β1和β3受体均与BAT中的腺苷酸环化酶偶联，新生动物BAT中腺苷酸环化酶的激活主要由β3受体介导。用β3选择性激动剂BRL 37344在断奶动物的BAT中也清楚地检测到了β3受体。然而，当使用儿茶酚胺刺激活性时，低浓度儿茶酚胺时发生的β1受体对腺苷酸环化酶的激活掩盖了仅在高浓度时发生的β3受体对腺苷酸环化酶的激活。
