MU-OPIOID RECEPTOR-MEDIATED REDUCTION OF LPHA-AMINO-3-HYDROXY-5-METHYL-4-ISOXAZOLEPROPIONIC ACID-ACTIVATED CURRENT IN DORSAL HORN NEURONS

Whole-cell voltage-clamp recording was used to examine the effects of mu-opioid receptor agonists DAGO (Tyr-D-Ala-Gly-MePhe-Gly-ol-enkephali n) and PL017 (Tyr-Pro-N-MePhe-D-Pro-NH2) on lpha-amino-3-hydroxy-5-met hyl-4-isoxazolepropionic acid (AMPA)-induced currents in acutely isola ted spinal dorsal horn (DH) neurons from laminae I-IV of young rats. W e found that the peak and steady-state amplitude of the AMPA-induced c urrent were depressed by mu-opioid agonists (1 nM-5 mu M) in a dose-de pendent manner in about 80% of the tested cells. When experiments were performed using whole-cell perforated patch technique, similar depres sion of AMPA current was produced by mu-opioids. The mu-opioid recepto r selective antagonist CTAP (100 nM) prevented or reduced the depressa nt effects of DAGO and PL017. Intracellular dialysis with guanosine 5' -O-(2-thiodiphosphate) (GDP-beta-S, 0.2 mM) significantly diminished t he PL017-induced depression of AMPA responses. In addition, when the c ells were dialyzed with guanosine 5'-0-(3-thiotriphosphate) (GTP-gamma -S, 0.1 mM) the amplitude and duration of the PL017-induced depression was significantly enhanced. Besides depressing the AMPA responses of DH cells, co-application of PL017 and kainic acid (KA) decreased the m agnitude of the KA-induced current in 60% of the tested cells. These r esults indicate that in acutely isolated rat DH neurons, the activatio n of mu-opioid receptor inhibits AMPA-activated current through activa tion of a G-protein. This action may contribute to the regulation of t he strength of the primary afferent neurotransmission including nocice ption.