Influence of calcium on the release of endogenous adenosine from spinal cord synaptosomes.
Intrathecal administration of Ca2+ has been shown to produce antinociception which is thought to be partially mediated by the release of adenosine. In the present study we have examined directly the effects of varying Ca2+ concentrations on the release of endogenous adenosine, measured by HPLC with fluorescence detection, from rat spinal cord synaptosomes. Although increasing the concentration of extracellular Ca2+ reduces the total amount of adenosine detected extrasynaptosomally, the component derived from the release of adenosine per se is actually augmented. This release of adenosine occurs from dorsal but not ventral spinal cord synaptosomes and appears to originate from capsaicin-sensitive nerve terminals. The Ca2+ ionophore A23187 also releases adenosine, but this release is due to the extrasynaptosomal conversion of released nucleotide(s) to adenosine, as it is markedly reduced by ecto-5'-nucleotidase inhibitors. Release of adenosine by A23187 occurs from both the dorsal and ventral spinal cord, and is not capsaicin-sensitive. Ethanol, used as a vehicle for the ionophore, releases adenosine which is a mixture of adenosine and nucleotide from both dorsal and ventral spinal cord synaptosomes. These observations provide direct support for behavioural studies which demonstrate that methylxanthines block antinociception produced by intrathecal administration of Ca2+.
Cahill
C M
CM
Department of Pharmacology, Dalhousie University, Halifax, Nova Scotia, Canada.
White
T D
TD
Sawynok
J
J
D000241:Adenosine / Q000378:metabolism*; D000704:Analysis of Variance; D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000008:administration & dosage / Q000494:pharmacology*; D002211:Capsaicin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004533:Egtazic Acid / Q000494:pharmacology; D000431:Ethanol / Q000494:pharmacology; D007278:Injections, Spinal; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000187:drug effects*; D013574:Synaptosomes / Q000187:drug effects* / Q000378:metabolism
D000001:Calcimycin; D000431:Ethanol; D004533:Egtazic Acid; D000241:Adenosine; D002211:Capsaicin; D002118:Calcium