T. Katsuragi et al., POSSIBLE TRANSSYNAPTIC CHOLINERGIC NEUROMODULATION BY ATP RELEASED FROM ILEAL LONGITUDINAL MUSCLES OF GUINEA-PIGS, Life sciences, 53(11), 1993, pp. 911-918
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.