Adenosine depresses spontaneous transmitter release from frog motor nerve terminals by acting at an A1-like receptor

Abstract

Adenosine (1[mu]M to 1mM) depressed spontaneous transmitter release from frog motor nerve terminals without producing any observable postsynaptic effects. Since this action of adenosine was blocked by 20[mu]M theophylline and 1[mu]M 8-phenyltheophylline, adenosine probably acts at a specific receptor on motor nerve terminals to reduce spontaneous transmitter output. The effects of the adenosine analogs, L-N6-phenylisopropyladenosine (L-PIA, 100pM to 1[mu]M), D-PIA (100nM to 100[mu]M), and 5'-N-ethylcarboxamidoadenosine (NECA, 10nM to 100[mu]M), were tested on spontaneous transmitter release at the frog neuromuscular junction. L-PIA The rank-order potency of these analogs indicates that adenosine acts at an A1-like receptor to depress spontaneous transmitter release. Inhibitory actions of maximally effective concentrations of adenosine and L-PIA were also blocked by the A1-specific antagonist, 1-3-dipropyl-8-cyclopentylxanthine (DPCPX) at a concentration of 100nM. Micromolar concentrations of NECA, an agonist with approximately equal affinity for the A1 and A2 receptors, produced biphasic effects on mepp frequency. Thus, a second adenosine receptor, perhaps of the A2 subtype, may be present on motor nerve terminals and may mediate an icnreaaspontaneous transmitter release. spontaneous transmitter release.