Fuller S J, Gaitanaki C J, Hatchett R J, Sugden P H
Department of Cardiac Medicine, National Heart and Lung Institute (University of London), U.K.
Biochem J. 1991 Jan 15;273(Pt 2)(Pt 2):347-53. doi: 10.1042/bj2730347.
In the presence of 5 microM-DL-propranolol and in HCO3(-)-containing buffers, 1 microM-adrenaline acutely stimulated protein synthesis by about 25% in the anterogradely perfused rat heart. This stimulation was opposed by low (1-10 nM) concentrations of prazosin, but not by similar concentrations of yohimbine, suggesting involvement of the alpha 1-adrenoceptor. Under the same conditions, adrenaline raised intracellular pH (pHi) by about 0.1 unit. The increase in pHi induced by adrenaline was prevented by 5 nM-prazosin, but not by 5 nM-yohimbine, again suggesting involvement of the alpha 1-adrenoceptor. Since an increase in pHi stimulates protein synthesis in the heart [Sugden & Fuller (1991) Biochem. J. 273, 339-346], the increase in pHi induced by adrenaline may be involved in its stimulation of protein synthesis. Adrenaline also increased phosphocreatine concentrations. As discussed, the increase in pHi induced by adrenaline may be responsible for this effect. Using second-order polynomial regression analysis, we showed that rates of protein synthesis were significantly correlated (P less than 0.0001) with phosphocreatine concentrations. We discuss two possible reasons for this correlation: (i) increases in pHi stimulate protein synthesis and separately raise phosphocreatine concentrations, or (ii) the increase in protein synthesis rates is a consequence of the raised phosphocreatine concentrations induced by the increase in pHi. Rates of protein synthesis were not significantly correlated with ATP/ADP concentration ratios, nor with any of the following: ATP, ADP, AMP or total adenine nucleotide concentrations. In freshly isolated adult rat cardiomyocytes, the protein kinase inhibitor staurosporine (1 microM) prevented stimulation of protein synthesis by 0.3 microM-adrenaline (and by 1 microM-phorbol 12-myristate 13-acetate or 1 m-unit of insulin/ml). The results are discussed within a mechanistic framework initiated by stimulation of the hydrolysis of membrane phospholipids by alpha 1-adrenergic agonists.
在存在5微摩尔-DL-普萘洛尔且在含HCO₃⁻的缓冲液中时，1微摩尔肾上腺素能在顺行灌注的大鼠心脏中急性刺激蛋白质合成约25%。低浓度（1 - 10纳摩尔）的哌唑嗪可对抗这种刺激，但类似浓度的育亨宾则无此作用，这表明α₁ - 肾上腺素能受体参与其中。在相同条件下，肾上腺素可使细胞内pH（pHi）升高约0.1个单位。5纳摩尔哌唑嗪可阻止肾上腺素诱导的pHi升高，但5纳摩尔育亨宾则不能，这再次表明α₁ - 肾上腺素能受体参与其中。由于pHi升高会刺激心脏中的蛋白质合成[Sugden & Fuller (1991) Biochem. J. 273, 339 - 346]，肾上腺素诱导的pHi升高可能与其对蛋白质合成的刺激有关。肾上腺素还会增加磷酸肌酸浓度。如前所述，肾上腺素诱导的pHi升高可能是造成这种效应的原因。使用二阶多项式回归分析，我们发现蛋白质合成速率与磷酸肌酸浓度显著相关（P < 0.0001）。我们讨论了这种相关性的两个可能原因：（i）pHi升高刺激蛋白质合成并分别提高磷酸肌酸浓度，或者（ii）蛋白质合成速率的增加是由pHi升高诱导的磷酸肌酸浓度升高的结果。蛋白质合成速率与ATP/ADP浓度比值无显著相关性，与以下各项也均无显著相关性：ATP、ADP、AMP或总腺嘌呤核苷酸浓度。在新鲜分离的成年大鼠心肌细胞中，蛋白激酶抑制剂星形孢菌素（1微摩尔）可阻止0.3微摩尔肾上腺素（以及1微摩尔佛波醇12 - 肉豆蔻酸酯13 - 乙酸酯或1毫单位/毫升胰岛素）对蛋白质合成的刺激。本文在由α₁ - 肾上腺素能激动剂刺激膜磷脂水解引发的机制框架内对结果进行了讨论。
