Diazepam enhances the inhibitory action of adenosine on transmission at the frog neuromuscular junction.
The effect of diazepam and its interaction with adenosine on evoked endplate potentials (e.p.p.s) and on twitch tension were investigated in innervated sartorius muscles of the frog. Diazepam (100 microM) reversibly decreased the amplitude of the e.p.p.s and the twitch responses evoked by indirect stimulation, and reversibly increased the resting membrane potential recorded from the endplates. In a concentration (30 microM) virtually devoid of an effect on the e.p.p.s, twitch responses, or resting membrane potential of the muscle fibres, diazepam potentiated the inhibitory action of adenosine on neuromuscular transmission, but not that induced by the stable analogue of adenosine 5'-N-ethylcarboxamide adenosine (NECA), which is not a substrate for the adenosine uptake system. The potentiating effect of diazepam was not observed in the presence of dipyridamole, an adenosine uptake blocker which potentiated the effect of adenosine on neuromuscular transmission. Diazepam shifted to the left the concentration-response curve obtained for adenosine in the presence of the adenosine receptor antagonist 8-phenyltheophylline (8-PT). The results suggest that diazepam acts at the frog neuromuscular junction by increasing the level of adenosine at the junction level; this increase probably results from inhibition in the uptake of the nucleoside.
De Mendonça
A
A
Laboratory of Pharmacology, Gulbenkian Institute of Science, Oeiras, Portugal.
Ribeiro
J A
JA
D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology*; D019830:Adenosine-5'-(N-ethylcarboxamide); D000818:Animals; D003975:Diazepam / Q000494:pharmacology*; D004176:Dipyridamole / Q000494:pharmacology; D004357:Drug Synergism; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D009045:Motor Endplate / Q000187:drug effects; D009119:Muscle Contraction / Q000187:drug effects; D009469:Neuromuscular Junction / Q000187:drug effects*; D011895:Rana ridibunda; D009435:Synaptic Transmission / Q000187:drug effects*; D013806:Theophylline / Q000031:analogs & derivatives / Q000494:pharmacology
D019830:Adenosine-5'-(N-ethylcarboxamide); D004176:Dipyridamole; D013806:Theophylline; C028322:8-phenyltheophylline; D000241:Adenosine; D003975:Diazepam