INHIBITORY AND EXCITATORY EFFECTS OF ADENOSINE RECEPTOR AGONISTS ON EVOKED TRANSMITTER RELEASE FROM PHRENIC-NERVE ENDINGS OF THE RAT

1 The effects of the adenosine analogues, 5'-N-ethyl-carboxamide adenosine (NECA), R-N6-phenylisopropyladenosine (R-PIA), 2-chloroadenosine (CADO), and CGS 21680C on electrically evoked tritium outflow from preparations loaded with [H-3]-choline and on evoked endplate potentials (e.p.ps), as well as the ability of the xanthines, 1,3-dipropyl-8-cyclopentylxanthine (DPCPX) and PD 115,199 to antagonize the effects of the adenosine analogues, were investigated in phrenic nerve-diaphragm preparations. 2 NECA, R-PIA and CADO decreased, in a concentration-dependent manner, the evoked tritium outflow from preparations loaded with [H-3]-choline. NECA and R-PIA were about equipotent and more potent than CADO. 3 DPCPX shifted to the right in a near parallel fashion the concentration-response curve for the inhibitory effect of R-PIA on evoked tritium outflow. 4 In the presence of DPCPX, NECA increased, rather than decreased, evoked tritium outflow. PD 115,199 antagonized, in a concentration-dependent manner, this excitatory effect of NECA. 5 CGS 21680C, in low nanomalar concentrations, increased evoked tritium outflow, an effect also antagonized by PD 115,199. 6 CGS 21680C increased, and R-PIA decreased, the amplitude of e.p.ps recorded from preparations paralysed with tubocurarine. Both effects could be observed in the same endplate. 7 It is concluded that both inhibitory (probably A1) and excitatory (probably A2) adenosine receptors coexist at the rat neuromuscular junction, modulating the evoked release of acetylcholine.