Functional Interaction Between Adrenergic Receptor Subtypes In the intracellular Signal Transduction.

在细胞内信号转导系统中，研究了特定放射性配基、G蛋白和第二信使的结合部位，研究了α和β肾上腺素能受体亚型之间可能的受体功能相互作用。(1)老年大鼠肾上腺素能受体数量减少的功能代偿机制：虽然心脏和大脑皮层α1肾上腺素能受体均减少，但α1肾上腺素能刺激诱导的肌醇磷酸酶在心脏中含量较低，在大脑皮层中含量较高。提示膜流动性的改变是细胞α-1肾上腺素能反应改变的部分原因。心脏和腮腺的β-肾上腺素能受体数量均减少。腺苷环化酶的活性状态是由于心脏Gs功能受损和腮腺细胞GI功能受损所致。(2)…在细胞内分布的变化对受体功能的影响更多的F离子：大鼠腮腺腺泡细胞内[Na~+]_i升高，[Ca~(2+)]_i升高，引起淀粉酶释放。而β-激动剂或二丁酰cAMP诱导的淀粉酶释放则受[Na~+]_i升高的抑制。[Na~+]_i升高不改变腺苷环化酶的活性，可能与细胞内cAMP功能的调节有关。(3)原代培养乳鼠心肌细胞发育过程中肾上腺素能受体功能的分析：β-肾上腺素能刺激引起的心率加快与细胞骨架结构的成熟是平行发展的。高浓度苯肾上腺素使心率加快，低浓度苯肾上腺素使心率减慢。α-1拮抗剂增强激动剂的刺激作用，但使激动剂的抑制作用减弱。用β-激动剂处理24小时，对高浓度的α-1激动剂的反应减弱，而对低浓度的反应强烈增强。较少

A possible interaction of receptor function between alpha- and beta-adrenergic receptor subtypes was studied about binding sites for specific radioligands, G proteins and second messengers in the intracellular signal transduction system. (1) Mechanism of functional compensation for a decrease of receptor number in the aged rats : Although alpha-1 adrenergic receptor decreased both in heart and cerebral cortex, the generation of inositol phosphates induced by alpha-1 adrenergic stimulation was low in heart and high in cerebral cortex. It was suggested that the change of membrane fluidity was partly responsible for the change of cellular alpha-1 adrenergic responses. The number of beta adrenergic receptors decreased both in heart and parotid gland. The states of activity of adenylate cyclase were resulted from the impairment of Gs function in hearts and the impairment of Gi function in parotid cells. (2) The modification of receptor function by the changes of intracellular distribution o … More f ions : An increased [Na^+] _i in rat parotid acinar cells caused the amylase release via the increase of [Ca^<2+>] _i . However, amylase release induced by beta-agonistOr dibutyryl cAMP was suppressed by the increased [Na^+] _i . Since the elevation of [Na^+] _i did not change adenylate cyclase activity, it may be responsible for the regulation of intracellular cAMP function. (3) Analysis of adrenergic receptor function of primary cultured neonatal rat cardiac myocytes during development : The increase of heart rate by beta-adrenergic stimulation developed in parallel with the maturation of cytoskeleton structure. The heart rate was increased by high concentration of phenylephrine, but decreased by its low concentration. Alpha-1 antagonist enhanced the stimulating effect of the agonist, but it caused a diminution of the suppressing effect of the agonist. Treatment with beta-agonist for 24 hours caused diminished response to high concentration of alpha-1 agonist and a strongly enhanced response to its lower concentration. Less