ATP release from dorsal spinal cord synaptosomes: characterization and neuronal origin

The present study determined the Ca(2+)-dependence of the release of adenosine 5'-triphosphate (ATP) from dorsal spinal cord synaptosomes evoked by depolarization with K+ and capsaicin, and the effect of intrathecal capsaicin pretreatment, dorsal rhizotomy and intrathecal pretreatment with 6-hydroxydopamine on such release. Release of ATP evoked by K+ was Ca(2+)-dependent, while that evoked by capsaicin was Ca(2+)-independent. Capsaicin pretreatment (60 micrograms, 7 days), which lesions small diameter afferents, did not alter release of ATP evoked by either K+ or capsaicin. Dorsal rhizotomy, which lesions all afferents, produced a significant reduction in the amount of ATP released from the rhizotomized side compared to the intact side. Pretreatment with 6-hydroxydopamine (100 micrograms, 7 days) to destroy adrenergic nerve terminals, markedly reduced 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 terminals in the spinal cord. ATP does not appear to originate from small diameter afferents as, although ATP is released by in vitro exposure to capsaicin, such release occurs only at high concentrations, release is Ca(2+)-independent and it is unaltered by pretreatment with capsaicin. The bulk of the ATP released from the spinal cord does not originate from descending noradrenergic nerve terminals.