Isoprenaline-induced increase in mRNA levels of inhibitory G-protein alpha-subunits in rat heart.

Long-term β-adrenergic stimulation has been shown to desensitize the β-adrenoceptor/adenylyl cyclase signalling pathway at both the receptor and the G-protein level. To further elucidate the cellular mechanism of G-protein regulation we investigated the influence of prolonged infusion of isoprenaline (2.4 mg/kg·d) on myocardial mRNA levels of different G-protein α-subunits in rats. For comparison rats were treated with triiodothyronine (T3; 0.5 mg/kg·d) which induces cardiac hypertrophy like isoprenaline but has different effects on the adenylyl cyclase system. Isoprenaline- and T3-treated animals developed an increase in heart/body weight ratio of 41±3% and 27±4%, respectively (P Giα-2-mRNA>Giα−3-mRNA and no detectable expression of Giα−1-mRNA in rat myocardium. mRNA levels of Gsα Giα−2 and Giα−3 were 36.9±1.28, 10.7±1.07 and 3.7±0.19 pg/μg total RNA, respectively. Isoprenaline increased Giα−2− and Giα−3-mRNA concentrations per μg total RNA by 49±18% and 27±710, respectively (P<0.05). This effect was abolished by simultaneously administered propranolol (9.9 mg/kg·d), indicating a,β-adrenoceptor-mediated mechanism. In contrast, T3-induced cardiac hypertrophy was not accompanied by changes in Giα-mRNA expression. Gsaα-mRNA levels were unaffected by either treatment.