Granneman J G
Department of Psychiatry, Wayne State University School of Medicine, Detroit, Michigan.
J Pharmacol Exp Ther. 1992 May;261(2):638-42.
The coupling of beta 1 and beta 3 adrenergic receptors to adenylyl cyclase was examined in membranes of isolated white adipocytes. The activation of adenylyl cyclase by isoproterenol (ISO) was biphasic. The high-affinity activation of adenylyl cyclase, which occurred at submicromolar concentrations of ISO, was mediated by beta 1 receptors, whereas low-affinity activation was mediated by beta 3 receptors. The relative activation of adenylyl cyclase by beta 3 receptors was less when ISO was used to stimulate activity, compared to when the beta 3-selective agonist BRL 37344 was used. These data indicate that both receptor subtypes can stimulate the same adenylyl cyclase in membranes of control cells, and that the activation of adenylyl cyclase by beta 1 receptors by low concentrations of catecholamines can obscure the activation by beta 3 receptors by high concentrations of catecholamines. Exposure of adipocytes to ISO at concentrations that either selectively stimulate beta 1 receptors or nonselectively stimulate both beta receptor subtypes greatly decreased the ability of beta 1, but not beta 3, receptors to activate adenylyl cyclase. In contrast, the exposure of cells to the beta 3-selective agonist BRL only slightly desensitized beta 1 receptors and did not affect beta 3 receptor activation of adenylyl cyclase. These data indicate that acute agonist exposure desensitizes beta 1, but not beta 3, receptors.
在分离的白色脂肪细胞膜中研究了β1和β3肾上腺素能受体与腺苷酸环化酶的偶联。异丙肾上腺素（ISO）对腺苷酸环化酶的激活呈双相性。在亚微摩尔浓度的ISO时发生的腺苷酸环化酶的高亲和力激活由β1受体介导，而低亲和力激活由β3受体介导。与使用β3选择性激动剂BRL 37344刺激活性相比，当使用ISO刺激活性时，β3受体对腺苷酸环化酶的相对激活作用较小。这些数据表明，两种受体亚型均可刺激对照细胞膜中的同一腺苷酸环化酶，并且低浓度儿茶酚胺通过β1受体对腺苷酸环化酶的激活可能会掩盖高浓度儿茶酚胺通过β3受体对其的激活。将脂肪细胞暴露于选择性刺激β1受体或非选择性刺激两种β受体亚型的浓度的ISO下，会大大降低β1受体（而非β3受体）激活腺苷酸环化酶的能力。相反，将细胞暴露于β3选择性激动剂BRL下只会使β1受体轻微脱敏，并且不会影响β3受体对腺苷酸环化酶的激活。这些数据表明，急性激动剂暴露会使β1受体而非β3受体脱敏。
