Adenosine suppresses the response of neurons to gaba in the superficial laminae of the rat spinal dorsal horn.
With the nystatin-perforated whole-cell patch-clamp recording technique, the modulatory effects of adenosine on GABA-activated whole-cell currents were investigated in neurons acutely dissociated from the superficial laminae (laminae I and II) of the rat spinal dorsal horn. The results showed that: (1) GABA acted on GABA(A) receptor and elicited inward Cl(-) currents (I(GABA)) at a holding potential (V(H)) of -40 mV; (2) adenosine suppressed GABA-induced Cl(-) current with affecting neither the reversal potential of I(GABA) nor the apparent affinity of GABA to its receptor; (3) N6-cyclo-hexyladenosine, a selective A(1) adenosine receptor agonist, mimicked the suppressing effect of adenosine on I(GABA), whereas 8-cyclopentyl-1,3-dipropylxanthine, a selective A(1) adenosine receptor antagonist, blocked the suppressing effect of adenosine; (4) chelerythrine, an inhibitor of protein kinase C, reduced the suppressing effect of adenosine on I(GABA); (5) pretreatment with 1,2-bis-(2-aminophenoxy) ethane-N,N,N',N'-tetraacetic acid tetrakis (acetoxy-methyl) ester, a Ca(2+) chelator, did not affect adenosine-induced suppression of I(GABA). The results indicate that: (1) the suppression of adenosine on I(GABA) is mediated by adenosine A(1) receptor and through a Ca(2+)-independent protein kinase C transduction pathway; (2) the interactions between adenosine and GABA might be involved in the modulation of nociceptive information transmission at spinal cord level.
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Department of Anatomy and K. K. Leung Brain Research Centre, Fourth Military Medical University, Xi'an 710032, China.
Li
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Li
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D000241:Adenosine / Q000819:agonists / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000470:Alkaloids; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D053119:Benzophenanthridines; D001640:Bicuculline / Q000494:pharmacology; D002614:Chelating Agents / Q000494:pharmacology; D004075:Diglycerides / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004533:Egtazic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D004553:Electric Conductivity; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018755:GABA Agonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D007546:Isoquinolines / Q000494:pharmacology; D008094:Lithium / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D009118:Muscimol / Q000494:pharmacology; D009433:Neural Inhibition / Q000187:drug effects; D018408:Patch-Clamp Techniques / Q000379:methods; D010617:Phenanthridines / Q000494:pharmacology; D020671:Posterior Horn Cells / Q000187:drug effects* / Q000502:physiology; D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D013449:Sulfonamides; D014970:Xanthines / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D000470:Alkaloids; D000700:Analgesics; D053119:Benzophenanthridines; D002614:Chelating Agents; D004075:Diglycerides; D004791:Enzyme Inhibitors; D018755:GABA Agonists; D018756:GABA Antagonists; D007546:Isoquinolines; D010617:Phenanthridines; D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D013449:Sulfonamides; D014970:Xanthines; D009118:Muscimol; D004533:Egtazic Acid; D005680:gamma-Aminobutyric Acid; C038237:1-oleoyl-2-acetylglycerol; D008094:Lithium; C051360:1,3-dipropyl-8-cyclopentylxanthine; C016299:chelerythrine; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; D000241:Adenosine; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide; D001640:Bicuculline