Abstract
The potential involvement of L- and N-type voltage-sensitive calcium (Ca2+) channels and a voltage-independent receptor-operated Ca2+ channel in the release of adenosine from dorsal spinal cord synaptosomes induced by depolarization with K+ and capsaicin was examined. Bay K 8644 (10 nM) augmented release of adenosine in the presence of a partial depolarization with K+ (addition of 6 mM) but not capsaicin (1 and 10 microM). This augmentation was dose dependent from 1 to 10 nM and was followed by inhibition of release from 30 to 100 nM. Nifedipine and nitrendipine inhibited the augmenting effect of Bay K 8644 in a dose-dependent manner, but neither antagonist had any effect on release of adenosine produced by K+ (24 mM) or capsaicin (1 and 10 microM). omega-Conotoxin inhibited K(+)-evoked release of adenosine in a dose-dependent manner but had no effect on capsaicin-evoked release. Ruthenium red blocked capsaicin-induced release of adenosine but had no effect on K(+)-evoked release. Although L-type voltage-sensitive Ca2+ channels can modulate release of adenosine when synaptosomes are partially depolarized with K+, N-type voltage-sensitive Ca2+ channels are primarily involved in K(+)-evoked release of adenosine. Capsaicin-evoked release of adenosine does not involve either L- or N-type Ca2+ channels, but is dependent on a mechanism that is sensitive to ruthenium red.
Highlights
Adenosine is an important inhibitory neuromodulator in the central nervous system
We have examined the role of L- and N-type voltagesensitive Ca” channel (VSCC) in depolarization-evoked release of adenosine from spinal cord synaptosomes
The DHPsensitive L-type Ca2+channel agonist Bay K 8644 had no significant effect on basal adenosine release
Summary
Adenosine is an important inhibitory neuromodulator in the central nervous system. In the spinal cord, adenosine plays a significant functional role in regulating nociceptive transmission (Sawynok and Sweeney, 1989).Release of adenosine contributes significantly to spinal antinociception by a number of agents including morphine and serotonin (DeLander and Hopkins, 1986, 1987; Sweeney et al, 1987, 1988), but the cellular mechanisms involved in such release are not well understood. W-Conotoxin inhibits Ca2+influx through the N-type VSCC and prevents release of neurotransmitters from the rat brain (Reynolds et al, 1986; Dooley et al, 1987)and spinal cord (Gandhi and Jones, 1990;Santicioli et al, 1992). Both L- and N-type Ca2+ channels have been implicated in neurotransmitter release from spinal cord preparations. We have examined the role of L- and N-type VSCCs in depolarization-evoked release of adenosine from spinal cord synaptosomes This was accomplished by determining the effects of DHP analogs (Bay K 8644, nifedipine, and nitrendipine) and w-conotoxin on K+- and capsaicin-evoked release of adenosine. The ability of ruthenium red to modify adenosine release evoked by K' and capsaicin was evaluated
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