Different roles of α1‐adrenoceptor subtypes in mediating cardiomyocyte protein synthesis in neonatal rats

Three different alpha1-adrenoceptor subtypes, designated alpha1A, alpha1B and alpha1D, have been cloned and identified pharmacologically in cardiomyocytes. In vitro studies have suggested that alpha1-adrenoceptors play an important role in facilitating cardiac hypertrophy. However, it remains controversial as to which subtype of alpha1-adrenoceptors is involved in this response. In the present study, we investigated the different role of each alpha1-adrenoceptor subtype in mediating cardiomyocyte protein synthesis, which is a most important characteristic of cardiac hypertrophy in cultured neonatal rat cardiomyocytes. 2. Cardiomyocyte hypertrophy was monitored by the following characteristic phenotypic changes: (i) an increase in protein synthesis; (ii) an increase in total protein content; and (iii) an increase in cardiomyocyte size. 3. The role of each alpha1-adrenoceptor subtype in mediating cardiomyocyte protein synthesis was investigated by the effect of specific alpha1-adrenoceptor subtype-selective antagonists on noradrenaline-induced [3H]-leucine incorporation. In addition, pKB values for alpha1-adrenoceptor subtype-selective antagonists were calculated and compared with the corresponding pKi values to further identify their effects. 4. Activation of alpha1-adrenoceptors by phenylephrine or noradrenaline in the presence of propranolol significantly increased [3H]-leucine incorporation, protein content and cell size. 5. Pre-incubating cardiomyocytes with 5-methyl-urapidil, RS 17053 or WB 4101 significantly inhibited noradrenaline-induced [3H]-leucine incorporation. However, there was no effect when cardiomyocytes were pre-incubated with BMY 7378. The correlation coefficients between pKB values for alpha1-adrenoceptor subtype-selective antagonists and pKi values obtained from cloned alpha1A-, alpha1B- or alpha1D-adrenoceptors were 0.92 (P <0.01), 0.66 (P >0.05) and 0.24 (P >0.05), respectively. 6. Our results suggest that the alpha1-adrenoceptor is dominantly responsible for adrenergic hypertrophy of cultured cardiomyocytes in neonatal rats. The efficiency in mediating cardiomyocyte protein synthesis is alpha1A > alpha1B >> alpha1D.