Relaxant effects of nucleotides in guinea pig isolated, perfused trachea: lack of involvement of prostanoids, Cl- channels and adenosine.
Tracheal segments from guinea-pigs were isolated, mounted to perfusion holders and connected via side hole catheters to differential pressure transducers. The pressure differences caused by the various agonists were measured and used to generate concentration response curves. Low concentrations of ATP contracted the trachea while high concentrations caused relaxation. ATP and beta-gamma-methylene-adenosine-triphosphate (APPCP) fully relaxed methacholine induced trachea. APPCP was a more potent relaxer than ATP, and both ATP and APPCP were more potent when applied extraluminally rather than intraluminally. Uracil-triphosphate had no relaxant ability, which suggested that relaxation was not mediated by a nucleotide receptor. 8-Phenyltheophylline (8-PT) added to the trachea baths did not inhibit either ATP or APPCP induced relaxation, indicating that relaxation was not caused by the metabolite of ATP, adenosine. Relaxation did not involve the formation of prostaglandins, since indomethacin had no effect on relaxation to ATP. Chlorine ion channels did not participate in relaxation, considering that 4,4-diisothiocyano-2,2-stilbene- disulfonate had no effect on maximum responses to ATP. The authors conclude that relaxation is mediated by an interaction of the adenine nucleotides with P2 purinoceptors and does not involve formed adenosine, prostaglandins or chlorine ion channels.