Adenosine and acetylcholine reduce isoproterenol-induced protein phosphorylation of rat myocytes.
Adenosine and acetylcholine reduce isoproterenol-induced protein phosphorylation of rat myocytes.
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腺苷和乙酰胆碱减少异丙肾上腺素诱导的大鼠肌细胞的蛋白质磷酸化。
DOI：
10.1016/0022-2828(91)90984-t
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发表时间：
1991
影响因子：
5
通讯作者：
DobsonJr,JG
中科院分区：
文献类型：
--
作者：
George,EE;Romano,FD;DobsonJr,JG
腺苷能和毒蕈碱剂已被证明可以减弱儿茶酚胺诱导的灌注心脏中蛋白磷酸化和收缩状态的增强。用苯异丙基腺苷（PIA）和氯化氨甲酰胆碱（CARB）对异丙肾上腺素（ISO）诱发的~（32）P掺入蛋白质底物的反应进行了研究，ISO（0.1 μm，30 s）使~（32）P掺入三种蛋白质底物（155，31，6 kD）的反应增加了8倍。当心肌细胞与PIA或CARB预孵育60 s时，1 μmPIA使31 kD和155 kD底物中ISO诱导的~（32）P掺入分别减弱37%和25%，而10 μmPIA仅减弱23%和11%。浓度为1 μmCARB时，这些相同底物的还原率分别为24%和17%，而浓度为10 μmCARB时，还原率分别为44%和50%。10 μ m心得安可拮抗ISO的作用。茶碱、磺苯茶碱和二丙基环戊基黄嘌呤可拮抗PIA的抑制作用，而阿托品可拮抗CARB的抑制作用。CARB对1 μmforskolin诱发的~（32）P参入的抑制作用大于PIA。此外，虽然PIA和CARB分别将ISO诱导的cAMP依赖性蛋白激酶（PKA）活性增加降低了48%和41%，但只有CARB减弱了ISO诱导的cAMP水平增加，使这种反应减弱了58%。结果表明，PIA在高浓度下减弱ISO诱导的~（32）P掺入的效果不如低浓度。此外，该化合物在减弱ISO的作用方面不如CARB有效。可以想象，这种差异可能与刺激性腺苷受体（A2）的激活和/或更大密度的毒蕈碱受体（包括多种抑制性毒蕈碱途径）有关。
Adenosinergic and muscarinic agents have been shown to attenuate the catecholamine-induced augmentation of both protein phosphorylation and contractile state in perfused hearts. The attenuation by phenylisopropyl-adenosine (PIA) and carbamylcholine chloride (CARB) of the isoproterenol (ISO)-induced incorporation of32P into protein substrates was examined in isolated rat ventricular myocytes.32P-labelled myocytes exposed to ISO (0.1 μm, 30 s) demonstrated up to an eight-fold increase of32P incorporation into three protein substrates (155, 31, 6 kD). When myocytes were pre-incubated with either PIA or CARB for 60 s, the ISO-induced32P incorporation in the 31 kD and the 155 kD substrates was attenuated 37% and 25%, respectively by 1 μmPIA and only 23% and 11%, by 10 μmPIA. A concentration of 1 μmCARB produced a 24% and 17% reduction in these same substrates while 10 μmCARB produced a 44% and 50% reduction. The effects of ISO were antagonized by 10 μmpropanolol. The inhibitory effects of PIA were antagonized by the theophylline, sulfophenyltheophylline and dipropylcyclopentylxanthine, whereas atropine antagonized the inhibitory effects of CARB. The32P incorporation elicited by 1 μmforskolin was reduced more by CARB than PIA. Additionally, while PIA and CARB reduced the ISO-induced increase in cAMP-dependent protein kinase (PKA) activity by 48% and 41% respectively, only CARB attenuated the ISO-elicited increase in cAMP levels, attenuating this response by 58%. The results indicate that PIA was less effective in attenuating ISO-induced32P incorporation at higher concentrations than at lower concentrations. Moreover, this compound was less potent than CARB at attenuating the effects of ISO. It is conceivable that this difference could be related to activation of stimulatory adenosine receptors (A2) and/or a greater density of muscarinic receptors including multiple inhibitory muscarinic pathways.