Adenosine selectively inhibits noncholinergic transmission in guinea pig bronchi

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Abstract
The neuromodulatory action of adenosine and ATP was investigated in isolated guinea pit bronchial strip chain preparations contracted with electrical field stimulation. The tissues were placed in organ baths containing physiological salt solution and stimulated at 8-Hz frequency, 0.5-ms pulse duration, and 30 V (.apprx.-100 mA) for 5 s. Electrical field stimulation evoked a biphasic contraction of bronchial muscle, consisting of an inital contraction followed by a sustained contraction, which was mediated by intramural cholinergic and noncholinergic nerve stimulations, respectively. Adenosine, at concentrations >10-6 M, caused a concentration-dependent inhibition in the height of the noncholinerfically mediated contraction, accompanied by a very weak inhibition on the cholinergically mediated response. ATP (10-5 to 3 .times. 10-3 M) also produced a similar inhibitory effect on the noncholinergically mediated contraction, but the inhibitory potency was less than that of adenosine. The inhibitory response to adenosine was enhanced by the pretreatment with dipyridamole, (2 .times. 10-6 M) but antagonized with aminophylline (10-5 M). Contractions of bronchial muscle with aminophylline (10-5 M). Conctractions of bronchial muscle evoked by exogenous acetylcholine (2 .times. 10-6 M) or substance P (2 .RTM. 10-7 M) were significantly inhibited by the adenosine (3 .times. 10-4 M) pretreatment. These data suggest that in isolated guinea pig bronchi adenosine selectively inhibits noncholinergic neurotransmission through prejunctional P1-purinoceptors.