INCREASED ACETYLCHOLINE CONTENT INDUCED BY ADENOSINE IN A SYMPATHETIC-GANGLION AND ITS SUBSEQUENT MOBILIZATION BY ELECTRICAL-STIMULATION

The present study was initiated to examine the effects of ATP on acety lcholine (ACh) synthesis. The exposure of superior cervical ganglia to ATP increased ACh stores by 25%, but this effect was also evident wit h ADP, AMP, and adenosine, but not with betagamma-methylene ATP, a non hydrolyzable analogue of ATP, or with inosine, the deaminated product of adenosine. Thus, we attribute the enhanced ACh content caused by AT P to the presence of adenosine derived from its hydrolysis by 5'-nucle otidase. The adenosine-induced increase of tissue ACh was not the cons equence of an adenosine-induced decrease of ACh release. The extra ACh remained in the tissue for more than 15 min after the removal of aden osine, but it was not apparent when ganglia were exposed to adenosine in a Ca2+-free medium. Incorporation of radiolabelled choline into [H- 3]ACh was also enhanced in the presence of adenosine, suggesting an ex tracellular source of precursor. Moreover, the synthesis of radiolabel led forms of phosphorylcholine and phospholipid was not reduced in ade nosine's presence, suggesting that the extra ACh was not likely derive d from choline destined for phospholipid synthesis. Aminophylline did not prevent the adenosine effect to increase ACh content; this effect was blocked by dipyridamole, but not by nitrobenzylthioinosine (NBTI). In addition, two benzodiazepine stereoisomers known to inhibit stereo selectively the NBTI-resistant nucleoside transporter displayed a simi lar stereoselective ability to block the effect of adenosine. Together , these results argue that adenosine is transported through an NBTI-re sistant nucleoside transporter to exert an effect on ACh synthesis. Th e extra ACh accumulated as a result of adenosine's action was releasab le during subsequent preganglionic nerve stimulation, but not in the p resence of vesamicol, a vesicular ACh transporter inhibitor. We conclu de that the mobilization of ACh is enhanced as a result of adenosine p retreatment.