MECHANISM OF ACTION OF ATP ON CANINE PULMONARY VAGAL C-FIBER NERVE-TERMINALS

1. The effects of extracellular adenosine 5'-triphosphate (ATP) on pul monary vagal afferent fibres (n = 46) was studied in a canine model in vivo (n = 38). 2. ATP (3-6 mu mol kg(-1)), administered as a rapid bo lus into the right atrium, elicited a transient burst of action potent ials in cervical vagal fibres, which was not affected by either blocka de of ganglionic transmission (hexamethonium) or a drop in arterial bl ood pressure (nitroglycerine). 3. The fibres with ATP-sensitive termin als were otherwise quiescent with no activity related to either cardia c or respiratory cycles and their conduction velocity was 0.85 +/- 0.1 3 m s(-1) (n = 7). 4. Inflation of the lungs to 2-3 times the tidal vo lume triggered brief bursts of action potentials in these fibres. 5. C apsaicin (10 mu g kg(-1)), given as a rapid bolus into the right atriu m, elicited a burst of action potentials in these ATP-sensitive fibres . 6. Smaller amounts of ATP and capsaicin (0.5-3 mu mol kg(-1) and 1-5 mu g kg(-1), respectively) had similar effects when the two compounds were given into the right pulmonary artery. 7. Adenosine, adenosine 5 '-monophosphate, or adenosine 5'-diphosphate did not excite these fibr es (n = 30). 8. The non-degradable analogue of ATP alpha,beta-methylen e ATP (alpha,beta-mATP) was tenfold more potent than ATP while beta,ga mma-methylene ATP (beta,gamma-mATP) was inactive. 9. The selective P-2 X-purinoceptor antagonist pyridoxalphosphate-6-azophenyl-2',4'-disulph onic acid markedly attenuated the effect of ATP but not of capsaicin. The P-2Y-purinoceptor antagonist Reactive Blue 2 was without effect. 1 0. Pretreatment with pertussis toxin (PTX) did not affect this action of ATP.11. In the canine lungs ATP activates vagal C fibre nerve termi nals. This action is mediated by P-2X-purinoceptors and is independent of a PTX-sensitive guanine nucleotide binding protein (G protein).