Modulation by adenosine of Adelta and C primary-afferent glutamatergic transmission in adult rat substantia gelatinosa neurons.
The present study examined the actions of adenosine on monosynaptic Adelta and C primary-afferent excitatory postsynaptic currents (EPSCs) recorded from substantia gelatinosa (SG) neurons of an adult rat spinal cord slice. In 67% of the neurons examined, adenosine reversibly decreased the amplitude of the Adelta-fiber EPSC, while in 13% of the neurons the amplitude was reduced or unaffected, which was followed by its increase persisting for several minutes after adenosine washout. The remaining neurons did not exhibit a change in the amplitude. The reduction in Adelta-fiber EPSC amplitude by adenosine was dose-dependent with an effective concentration for half-inhibition (EC50) value of 217 microM. When examined by using a paired-pulse stimulus, a ratio of the second to first Adelta-fiber EPSC amplitude under the reduction was larger than that of EPSC amplitude in the control, suggesting a presynaptic action of adenosine. In 69% of the neurons tested, the C-fiber EPSC was reversibly decreased in amplitude by adenosine (100 microM) by an extent comparable to that of Adelta-fiber EPSC; the remaining neurons were without adenosine actions. Similar inhibitory actions of adenosine were also seen in neurons where both Adelta-fiber and C-fiber EPSCs were elicited. Similar reduction in the Adelta-fiber or C-fiber EPSC amplitude was induced by an A1 adenosine-receptor agonist, N6-cyclopentyladenosine (1 microM), and the adenosine-induced reduction was not observed in the presence of an A1 antagonist, 8-cyclopentyl-1,3-dipropylxanthine (1 microM). An A2a agonist, CGS 21680 (1 microM), did not significantly affect the Adelta-fiber EPSC amplitude. It is concluded that adenosine presynaptically inhibits monosynaptic Adelta-fiber and C-fiber transmission by a similar extent through the activation of the A1 receptor in many but not all SG neurons; this could contribute to at least a part of antinociception by intrathecally administered adenosine analogues and probably by endogenous adenosine.
Lao
L-J
LJ
Department of Physiology, Saga Medical School, 5-1-1 Nabeshima, Saga 849-8501, Japan.
Kawasaki
Y
Y
Yang
K
K
Fujita
T
T
Kumamoto
E
E
D000241:Adenosine / Q000378:metabolism*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D005973:Glutamine / Q000378:metabolism*; D008297:Male; D009475:Neurons, Afferent / Q000187:drug effects / Q000378:metabolism*; D009924:Organ Culture Techniques; D010146:Pain / Q000503:physiopathology; D018408:Patch-Clamp Techniques; D058915:Purinergic P1 Receptor Antagonists; D051381:Rats; D017207:Rats, Sprague-Dawley; D018047:Receptors, Purinergic P1 / Q000378:metabolism; D013376:Substantia Gelatinosa / Q000187:drug effects / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*
D058915:Purinergic P1 Receptor Antagonists; D018047:Receptors, Purinergic P1; D005973:Glutamine; D000241:Adenosine