The present study determined the Ca2+-dependence of the release of ade
nosine 5'-triphosphate (ATP) from dorsal spinal cord synaptosomes evok
ed by depolarization with K+ and capsaicin, and the effect of intrathe
cal capsaicin pretreatment, dorsal rhizotomy and intrathecal pretreatm
ent with 6-hydroxydopamine on such release. Release of ATP evoked by K
+ was Ca2+-dependent, while that evoked by capsaicin was Ca2+-independ
ent. Capsaicin pretreatment (60 mug, 7 days), which lesions small diam
eter afferents, did not alter release of ATP evoked by either K+ or ca
psaicin. Dorsal rhizotomy, which lesions all afferents, produced a sig
nificant reduction in the amount of ATP released from the rhizotomized
side compared to the intact side. Pretreatment with 6-hydroxydopamine
(100 mug, 7 days) to destroy adrenergic nerve terminals, markedly red
uced spinal cord noradrenaline levels, but did not alter the K+-evoked
release of ATP. These results suggest that some K+-evoked release of
ATP could originate from large but not small diameter afferent nerve t
erminals in the spinal cord. ATP does not appear to originate from sma
ll diameter afferents as, although ATP is released by in vitro exposur
e to capsaicin, such release occurs only at high concentrations, relea
se is Ca2+-independent and it is unaltered by pretreatment with capsai
cin. The bulk of the ATP released from the spinal cord does not origin
ate from descending noradrenergic nerve terminals.