Correlation between the effects of salbutamol on contractions and cyclic AMP content of isolated fast-and slow-contracting muscles of the guinea pig

Abstract

The effects of isoprenaline and salbutamol on incomplete tetanic contractions of the isolated soleus (slow contracting) and extensor digitorum longus (EDL-fast-contracting) muscles of the guinea pig were studied and an attempt made to correlate these effects on contractility with changes in cyclic AMP concentrations. Salbutamol was 10-12 times less potent than (+/-)isoprenaline in decreasing the force of subtetanic contractions in the soleus and between 5-6 times less potent in increasing the force of subtetanic contractions in the EDL. This observation plus the lack of activity of both the selective beta1-adrenoceptor antagonist (atenolol) and the selective beta1 agonist (H 133/22) in the EDL implies involvement of beta2-adrenoceptors in these responses of the muscles to isoprenaline and salbutamol. The soleus muscle was about 6-12 times more sensitive to effects of beta-adrenoceptor agonists than the EDL. In concentrations which produced effects on muscle contractility, salbutamol significantly elevated cyclic AMP concentrations in both types of muscle. These effects were antagonised by propranolol. It seems clear that the contrasting effects of sympathomimetic amines on slow-and fast contracting muscle are mediated through a common mechanism-elevation of cyclic AMP. Possible explanations of this apparent paradox are discussed.