Rapid changes in rat pineal beta-adrenergic receptor: alterations in l-(3H)alprenolol binding and adenylate cyclase.
Rapid changes in rat pineal beta-adrenergic receptor: alterations in l-(3H)alprenolol binding and adenylate cyclase.
复制标题
大鼠松果体β-肾上腺素能受体的快速变化：l-(3H)阿普洛尔结合和腺苷酸环化酶的变化。
DOI：
10.1073/pnas.72.9.3735
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发表时间：
1975
影响因子：
11.1
通讯作者：
J. Axelrod
中科院分区：
文献类型：
--
作者：
J. Kebabian;M. Zatz;J. A. Romero;J. Axelrod
调节松果体中腺苷酸环化酶[ATP焦磷酸裂解酶（环化）8 EC 4.6.1.1]的β-肾上腺素能受体的性质与特异性结合l-[3 H]阿普洛尔（一种有效的β-肾上腺素能拮抗剂）的位点的性质相似。β-肾上腺素能受体的刺激导致N-乙酰基转移酶（=芳胺乙酰基转移酶;乙酰CoA：芳胺N-乙酰基转移酶，EC 2.3.1.5）活性增加30倍，N-乙酰基转移酶是一种参与松果体激素褪黑激素合成的酶。在正常的昼夜光暗周期中，松果体中的β-肾上腺素能受体在夜间比在白天有更大的生理刺激。在恒定光照下保持24小时的大鼠的松果体比在黑暗中保持过夜的大鼠的松果体具有更高的腺苷酸环化酶敏感性，并且特异性地结合更多的l-[3 H]阿普洛尔。当大鼠暴露于光照24小时，用肾上腺素能激动剂异丙肾上腺素治疗时，有一个快速损失的腺苷酸环化酶活性和特定的l-[3 H]阿普洛尔结合位点。腺苷酸环化酶对异丙肾上腺素或其底物ATP的亲和力没有变化。类似地，尽管结合位点较少，但其余位点对激动剂或拮抗剂的亲和力没有变化。用放线菌酮抑制蛋白质合成不影响腺苷酸环化酶活性或特异性结合位点的丧失。这些数据表明，β-肾上腺素能受体的刺激会导致可用受体的数量和对腺苷酸敏感的腺苷酸环化酶活性迅速减少;相反，缺乏刺激会导致这些参数增加。这表明，这些变化有助于超和次敏感性的现象，在松果体中通过调节松果体的能力，合成环AMP响应β-肾上腺素能刺激。
The properties of the beta-adrenergic receptor which regulates adenylate cyclase [ATP pyrophosphate-lyase (cyclizing)8 EC 4.6.1.1] in the pineal gland are similar to the properties of the sites which specifically bind l-[3H]alprenolol, a potent beta-adrenergic antagonist. Stimulation of the beta-adrenergic receptor results in a 30-fold increase in the activity of N-acetyltransferase (= arylamine acetyltransferase; acetyl CoA:arylamine N-acetyltransferase, EC 2.3.1.5), an enzyme involved in the synthesis of thepineal hormone melatonin. In the normal diurnal light-dark cycle there is greater physiological stimulation of the beta-adrenergic receptor in the pineal during the night than during the day. Pineals from rats kept in constant light for 24 hr possess more hormone-sensitive adenylate cyclase and specifically bind more l-[3H]alprenolol than do pineals from rats kept in the dark overnight. When rats, exposed to light for 24 hr, are treated with the beat-adrenergic agonist isoproterenol, there is a rapid loss of both hormone-sensitive adenylate cyclase activity and specific l-[3H]alprenolol binding sites. There is no change in the affinity of adenylate cyclase for isoproterenol or for its substrate, ATP. Similarly, although there are fewer binding sites, there is no change in the affinity of the remaining sites for either agonist or antagonist. Inhibition of protein synthesis with cycloheximide does not affect the loss of either adenylate cyclase activity or specific binding sites. The data suggest that stimulation of the beta-adrenergic receptor causes a rapid decrease in the number of available receptors and in hormone-sensitive adenylate cyclase activity; conversely, lack of stimulation causes an increase in these parameters. It is suggested that these changes contribute to the phenomena of super- and subsensitivity in the pineal gland by regulating the capacity of the pineal to synthesize cyclic AMP in response to beta-adrenergic stimulation.