Adenosine triphosphate (ATP) has been proposed to play a role as a neurotra
nsmitter in the retina, but not much attention has been given to the regula
tion of ATP release from retinal neurons. In this work, we investigated the
release of ATP from cultures enriched in amacrine-like neurons. Depolariza
tion of the cells with KCl, or activation of alpha-amino-3-hydroxy-5-methyl
-4-isoxazole-propionate (AMPA) receptors, evoked the release of ATP, as det
ermined by the luciferin/luciferase luminescent method. The ATP release was
found to be largely Ca2+ dependent and sensitive to the botulinum neurotox
in A, which indicates that the ATP released by cultured retinal neurons ori
ginated from an exocytotic pool. Nitrendipine and omega-Agatoxin IVA, but n
ot by omega-Conotoxin GVIA, partially blocked the release of ATP, indicatin
g that in these cells, the Ca2+ influx necessary to trigger the release of
ATP occurs in part through the L- and the P/Q types of voltage-sensitive Ca
2+ channels (VSCC), but not through N-type VSCC, The release of ATP increas
ed in the presence of adenosine deaminase, or in the presence of 1,3-diprop
yl-8-cyclopentylxanthine (DPCPX), an adenosine A(1) receptor antagonist, sh
owing that the release is tonically inhibited by the adenosine A(1) recepto
rs. To our knowledge, this is the first report showing the release of endog
enous ATP from a retinal preparation. (C) 1999 John Wiley & Sons. Inc.