AMINOPHYLLINE ENHANCES RESTING CA2-PIPIENS( CONCENTRATIONS AND TWITCHTENSION BY ADENOSINE RECEPTOR BLOCKADE IN RANA)

We hypothesized that the xanthine aminophylline acts to Mock adenosine receptors on the surface of skeletal muscle fibres, thereby inhibitin g 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 (P-t) of the semitendinosus muscle in normal frog Ringer solution (NFR) ranged from 6.8 to 9.4 g. Intracellular Ca2+ con centrations in control resting fibres ranged from 67 to 70 nM. Aminoph ylline at 100 M mu produced increases of 26 and 22% in P-t and Ca2+ co ncentrations, respectively. 3. The adenosine receptor antagonists 8-ph enyltheophylline (8-PT) and 1,3-dipropyl-7-methylxanthine (1,3-d-7-M) both increased P-t by 32% over values in NFR. In addition, 1,3-d-7-M i ncreased resting Ca2+ concentrations by 29% over control levels. 4. Ad enosine deaminase increased twitch tension and resting intracellular C a2+ concentrations by 22 and 26% over controls, respectively. 5. N-6-( 2-phenylisopropyl)adenosine (R-PIA, 1 mu M), a potent adenosine analog ue, partially blocked both the increase in P,and intracellular Ca2+ co ncentrations induced by the xanthines, possibly by competing for the a denosine receptor. 6. The data herein provide support for the existenc e of adenosine receptors on the membranes of skeletal muscle fibres an d suggest a possible role for adenosine receptors in the regulation of twitch tension.