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

细胞内信号转导中肾上腺素能受体亚型之间的功能相互作用。

• 批准号: 01570110
• 负责人: OHSHIKA Hideyo
• 金额: $ 1.34万
• 依托单位: Sapporo Medical College
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1989
• 资助国家: 日本
• 起止时间: 1989 至 1990
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-01570110/
• 关键词: Adrenergic Receptors; Aging; G Proteins; Cultured Myocytes; Intracellular Sodium Ion; Inositol Phosphates; 耳下腺; アミラ-ゼ放出; 細胞内カルシウム; モネンシン; GTP結合蛋白; アデニレ-トシクラ-ゼ; フォスホリパ-ゼC活性; フォスフォリパ-ゼA_2活性; 加令

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

研究了α-和β-肾上腺素能受体亚型在细胞内信号转导系统中特异性放射性配体、G蛋白和第二信使的结合位点之间可能的受体功能相互作用。(1)老年大鼠受体数量减少的功能代偿机制：虽然心脏和大脑皮质α 1肾上腺素能受体减少，但α 1肾上腺素能刺激诱导的磷酸肌醇产生在心脏低，在大脑皮质高。提示细胞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β肾上腺素能受体数量减少。腺苷酸环化酶的活性状态与心脏Gs功能受损和腮腺细胞Gi功能受损有关。(2)细胞内分布的改变对受体功能的影响 ...更多信息 f离子：[Na^+] i增加可通过[Ca^<2+] i增加引起大鼠腮腺腺泡细胞淀粉酶释放。而β激动剂或二丁酰cAMP诱导的淀粉酶释放则被[Na^+] _i升高所抑制。由于[Na^+] i的升高并不改变腺苷酸环化酶的活性，因此它可能是调节细胞内cAMP功能的原因。(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增加与细胞骨架结构的成熟平行发展。高浓度苯乙哌啶使心率加快，低浓度苯乙哌啶使心率减慢。α 1受体拮抗剂增强激动剂的兴奋作用，但减弱激动剂的抑制作用。用β-激动剂处理24小时导致对高浓度α-1激动剂的反应减弱，对其低浓度的反应强烈增强。少

项目成果

木村 永一: "Simple isolation method of neonatal rat cardiac myocytes and the development of primary culture of cardiac myocyte in culture" In Vitro.

Eiichi Kimura：“新生大鼠心肌细胞的简单分离方法以及心肌细胞原代培养物的体外培养”。

宮本 篤: "Age‐related changes in ^3H prazosin binding and phosphoinositide hydrolysis in rat ventricular myocardium" Gen.pharmac.20. 647-651 (1989)

Atsushi Miyamoto：“大鼠心室心肌中 ^3H 哌唑嗪结合和磷酸肌醇水解的年龄相关变化”Gen.pharmac.20 (1989)。

TAKEMURA, HARUO: "Mechanism of activation of the receptor operated calcium influx in non-excitable cells." Folia Pharmacologica Japonica. vll. 97. (1991)

TAKEMURA, HARUO：“受体激活机制控制非兴奋性细胞中的钙流入。”

宮本 篤: "Membrane viscosity correlates with ーadrenergic signal transduction of the aged rat cerebral cortex" J.Neurochem.55. 70-75 (1990)

Atsushi Miyamoto：“膜粘度与老年大鼠大脑皮层的β-肾上腺素能信号转导相关”J.Neurochem.55 (1990)。

MIYAMOTO, ATUSHI: "Age-related changes in ^3H prazosin binding and phosphoinositide hydrolysis in rat ventricular myocardium." Gen. Pharmac.20. 647-651 (1989)

MIYAMOTO, ATUSHI：“大鼠心室心肌中 ^3H 哌唑嗪结合和磷酸肌醇水解的年龄相关变化。”