Wolfe B B, Harden T K, Molinoff P B
Proc Natl Acad Sci U S A. 1976 Apr;73(4):1343-7. doi: 10.1073/pnas.73.4.1343.
The response of rat liver adenylate cyclase [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1] to catecholamines is enhanced after adrenalectomy. To investigate this phenomenon, we developed an in vitro assay for beta-adrenergic receptors of plasma membranes derived from livers of control and adrenalectomized rats, using [125I]iodohydroxybenzylpindolol (IHYP), a potent beta-adrenergic receptor antagonist. Binding of IHYP reached equilibrium within 30 min and dissociation occurred with a half-time of approximately 60 min. The l-isomers of isoproterenol and propranolol were at least 50 times more potent as inhibitors of IHYP binding than were the corresponding d-isomers. Adrenalectomy did not affect the rates of association or dissociation of IHYP or the dissociation constants of several ligands that are active at beta-adrenergic receptors. The number of binding sites for IHYP was determined in homogenates and in purified membranes of livers from control and adrenalectomized rats. The number of sites increased 3- to 5-fold after adrenalectomy. A similar increase in hormone stimulation of adenylate cyclase was observed. These changes were reversed by the administration of cortisone. The increase in the number of binding sites for IHYP may be a compensatory response to the impairments in gluconeogenesis and glycogenolysis which occur after adrenalectomy.
肾上腺切除术后，大鼠肝脏腺苷酸环化酶[ATP焦磷酸裂解酶（环化），EC 4.6.1.1]对儿茶酚胺的反应增强。为了研究这一现象，我们利用强效β-肾上腺素能受体拮抗剂[125I]碘羟基苄基吲哚洛尔（IHYP），开发了一种体外测定对照大鼠和肾上腺切除大鼠肝脏来源质膜β-肾上腺素能受体的方法。IHYP的结合在30分钟内达到平衡，解离的半衰期约为60分钟。异丙肾上腺素和普萘洛尔的l-异构体作为IHYP结合抑制剂的效力至少是相应d-异构体的50倍。肾上腺切除术不影响IHYP的结合或解离速率，也不影响几种对β-肾上腺素能受体有活性的配体的解离常数。在对照大鼠和肾上腺切除大鼠肝脏的匀浆和纯化膜中测定了IHYP的结合位点数量。肾上腺切除术后，位点数量增加了3至5倍。观察到腺苷酸环化酶的激素刺激也有类似增加。给予可的松后，这些变化得以逆转。IHYP结合位点数量的增加可能是对肾上腺切除术后糖异生和糖原分解受损的一种代偿反应。
