POSSIBLE TRANSSYNAPTIC CHOLINERGIC NEUROMODULATION BY ATP RELEASED FROM ILEAL LONGITUDINAL MUSCLES OF GUINEA-PIGS

The effects of alpha,beta-methylene ATP (alpha,beta-mATP) and beta,gam ma-methylene ATP (beta,gamma-mATP) on endogenous acetylcholine (ACh) r elease evoked by electrical nerve stimulation were evaluated in guinea -pig ileal longitudinal muscles. Release of ACh was measured with an H PLC-electrochemical detector system and release of ATP by luciferin-lu ciferase assay. Electrically evoked endogenous ACh release was reduced by both alpha,beta-mATP and beta,gamma-mATP at concentrations of 3 an d 30 muM. The inhibitory effect of alpha,beta-mATP (30 muM) on ACh rel ease was not detectable in the presence of theophylline (100 muM), a P 1-purinoceptor antagonist, that itself enhanced ATP release. When exog enous ATP (0.1 muM) was added to the bath in which the ileal segment w as suspended, it was rapidly metabolized, presumably by ecto-ATPase, a nd disappeared from the medium within 15 min. At.30 muM, alpha,beta-mA TP induced ATP release in a suramin-sensitive but Ca2+- and atropine-i nsensitive manner, suggesting P2-receptor-mediated release of ATP from the smooth muscle. We conclude from these findings that alpha,beta-mA TP and, probably,also beta,gamma-mATP, do not reduce ACh release by di rect stimulation of presynaptic P1-purinoceptors, and that endogenous ATP released postjunctionally by these ATP analogs is decomposed metab olically to adenosine in the synapse and this adenosine triggers P1-pu rinoceptor sensitive neuromodulation of cholinergic transmission.