Adenosine suppresses GABAA receptor-mediated responses in rat sacral dorsal commissural neurons.
The modulatory effect of adenosine on gamma-aminobutyric acid (GABA)-activated whole-cell currents were investigated in the neurons acutely dissociated from the rat sacral dorsal commissural nucleus (SDCN) using the nystatin perforated patch recording configuration under the voltage-clamp conditions. The results showed that: (1) GABA acted on GABAA receptor and elicited inward Cl- currents (IGABA) at a holding potential (VH) of -40 mV; (2) adenosine suppressed GABA-induced Cl- current without affecting the reversal potential of IGABA and the apparent affinity of GABA to its receptor; (3) N6-cyclohexyladenosine mimicked the suppression effect of adenosine on IGABA, whereas 8-cyclopentyl-1,3-dipropylxanthine blocked the suppression effect of adenosine; (4) adenosine fails to suppress IGABA on the neurons that were pretreated with bisindolylmaleimide I (BIM), while after pretreatment with H-89, the inhibitory effect of adenosine on IGABA were not affected; (5) the suppression effect of adenosine on IGABA remained in the presence of BAPTA-AM. The present results indicate that the suppression of adenosine on IGABA is mediated by adenosine A1 receptor and through a Ca2+-independent protein kinase C transduction pathway, and that the interactions between adenosine and GABA might participate in the modulation of nociceptive information transmission at the SDCN.
Li
Hui
H
Department of Anatomy and K.K. Leung Brain Research Centre, The Fourth Military Medical University, No. 17, W. Chang-le Road, Xi'an 710032, PR China.
Wu
Le
L
Li
Yun-Qing
YQ
D000241:Adenosine / Q000494:pharmacology*; D000818:Animals; D002712:Chlorides / Q000378:metabolism; D018682:GABA Agents / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000378:metabolism*; D018047:Receptors, Purinergic P1 / Q000378:metabolism; D012445:Sacrococcygeal Region; D013116:Spinal Cord / Q000166:cytology*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D002712:Chlorides; D018682:GABA Agents; D011963:Receptors, GABA-A; D018047:Receptors, Purinergic P1; D005680:gamma-Aminobutyric Acid; D000241:Adenosine