Aminophylline enhances resting Ca2+ concentrations and twitch tension by adenosine receptor blockade in Rana pipiens

1. We hypothesized that the xanthine aminophylline acts to block adenosine receptors on the surface of skeletal muscle fibres, thereby inhibiting a depressant action of endogenous adenosine. We further hypothesized that this action results in increased concentrations of intracellular resting Ca2+ and enhanced twitch tension upon muscle stimulation. 2. Peak twitch tension (Pt) of the semitendinosus muscle in normal frog Ringer solution (NFR) ranged from 6.8 to 9.4 g. Intracellular Ca2+ concentrations in control resting fibres ranged from 67 to 70 nM. Aminophylline at 100 microM produced increases of 26 and 22% in Pt and Ca2+ concentrations, respectively. 3. The adenosine receptor antagonists 8-phenyltheophylline (8-PT) and 1,3-dipropyl-7-methylxanthine (1,3-d-7-M) both increased Pt by 32% over values in NFR. In addition, 1,3-d-7-M increased resting Ca2+ concentrations by 29% over control levels. 4. Adenosine deaminase increased twitch tension and resting intracellular Ca2+ concentrations by 22 and 26% over controls, respectively. 5. N6-(2-phenylisopropyl)adenosine (R-PIA, 1 microM), a potent adenosine analogue, partially blocked both the increase in Pt and intracellular Ca2+ concentrations induced by the xanthines, possibly by competing for the adenosine receptor. 6. The data herein provide support for the existence of adenosine receptors on the membranes of skeletal muscle fibres and suggest a possible role for adenosine receptors in the regulation of twitch tension.