THE ROLE OF ENDOGENOUS ADENOSINE IN A POSTSTIMULATION INCREASE IN THEACETYLCHOLINE CONTENT OF A SYMPATHETIC-GANGLION

Previous experiments showed that exposure of sympathetic ganglia to ex ogenous adenosine increased acetylcholine (ACh) content and its subseq uent release. This effect was not mediated through extracellular adeno sine receptors, but at an intracellular site following its uptake thro ugh nitrobenzylthioinosine (NBTI)-resistant nucleoside transporters. W e postulated that endogenous adenosine may play a role in modulating s ynaptic transmission in the superior cervical ganglion. The present st udy tested whether adenosine is involved in the activation of ACh synt hesis that occurs during a rest period following prolonged presynaptic tetanic activity. Conditioning of ganglia with high-frequency stimula tion (15 Hz) for 45 min followed by a 15 min rest increased their ACh content by 45%. The appearance of this ''rebound ACh'' showed sensitiv ity to nucleoside transport inhibitors; it was prevented by dipyridamo le, but not by NBTI or meclonazepam, and it was reduced in the presenc e of RO 11-3624, suggesting an involvement of NBTI-resistant transport ers. The effect of dipyridamole was specific for the synthesis of rebo und ACh in that it did not inhibit ACh release or ACh synthesis during stimulation. The inhibitory action of dipyridamole on the synthesis o f rebound ACh was not evident if it was present only during the tetani c stimulation but it was if dipyridamole was present during the rest p eriod following it, suggesting that adenosine's presence after tetanic stimulation is of importance. This conclusion was strengthened by exp eriments showing that the presence of cyclopentyl-theophylline, an ant agonist at inhibitory adenosine receptors, increased ACh output evoked by test stimulation immediately following tetanic activity, as if end ogenous adenosine was available at that time to activate the adenosine receptors that inhibit transmitter release. ACh release from conditio ned ganglia was 44% greater than that from the controls. However, the rebound ACh was not mobilized in the presence of 2-(4-phenylpiperidino )cyclohexanol (vesamicol), a vesicular ACh transporter inhibitor. Thes e results suggest that endogenous adenosine released after tetanic sti mulation activates ACh synthesis, which results in an increase of gang lionic ACh that is available for subsequent mobilization and release.