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Inhibition of muscarinic stimulated phosphoinositide hydrolysis in the rat parotid gland by cAMP.

机译:cAMP在鼠腮腺中抑制毒蕈碱刺激的磷酸肌醇水解。

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摘要

The ability of agents that increase or mimic cAMP to affect muscarinic receptor mediated phosphoinositide hydrolysis was investigated in the rat parotid gland. Forskolin (10 microM) and isoproterenol (10 microM) elevated cAMP in the parotid gland by 2-fold and 7-fold, respectively, and these agents also inhibited oxotremorine-M (3 microM) mediated phosphoinositide hydrolysis by 14% and 26%, respectively. Forskolin (1, 4.3, 18, and 75 microM) increased cAMP accumulation and inhibited PIP2 hydrolysis in a concentration-dependent manner. Forskolin (75 micrometers) shifted the concentration-response curve for the full agonist oxotremorine-M rightward by 4.2-fold. Pre-treatment with the phosphodiesterase inhibitor isobutylmethylxanthine (1 mM) reduced the maximum effect of oxotremorine-M by 31%. The inhibitory effect of isoproterenol and forskolin on muscarinic receptor-mediated phosphoinositide hydrolysis was unaffected by the removal of extracellular Ca2+. Moreover, isoproterenol and forskolin dampened sodium fluoride and oxotremorine-M mediated phosphoinositide hydrolysis to the same extent suggesting that the inhibitory effect of cAMP is downstream from the muscarinic receptor.
机译:在大鼠腮腺中研究了增加或模拟cAMP的药物影响毒蕈碱受体介导的磷酸肌醇水解的能力。 Forskolin(10 microM)和异丙基肾上腺素(10 microM)将腮腺中的cAMP分别提高了2倍和7倍,并且这些药物还抑制了氧代雷莫林-M(3 microM)介导的磷酸肌醇水解,分别为14%和26%,分别。 Forskolin(1、4.3、18和75 microM)以浓度依赖性方式增加cAMP积累并抑制PIP2水解。 Forskolin(75微米)将完整激动剂oxotremorine-M的浓度响应曲线右移4.2倍。用磷酸二酯酶抑制剂异丁基甲基黄嘌呤(1 mM)进行预处理可使oxotremorine-M的最大作用降低31%。异丙肾上腺素和福司可林对毒蕈碱受体介导的磷酸肌醇水解的抑制作用不受细胞外Ca2 +去除的影响。而且,异丙肾上腺素和毛喉素对氟化钠和氧代反刍素-M介导的磷酸肌醇的水解作用具有相同程度的抑制作用,表明cAMP的抑制作用在毒蕈碱受体的下游。

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