mu-Opioid receptor-mediated reduction of alpha-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-enkephalin) and PL017 (Tyr-Pro-N-MePhe-D-Pro-NH2) on alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-induced currents in acutely isolated spinal dorsal horn (DH) neurons from laminae I-IV of young rats. We found that the peak and steady-state amplitude of the AMPA-induced current were depressed by mu-opioid agonists (1 nM-5 microM) in a dose-dependent manner in about 80% of the tested cells. When experiments were performed using whole-cell perforated patch technique, similar depression of AMPA current was produced by mu-opioids. The mu-opioid receptor selective antagonist CTAP (100 nM) prevented or reduced the depressant effects of DAGO and PL017. Intracellular dialysis with guanosine 5'-O-(2-thiodiphosphate) (GDP-beta-S, 0.2 mM) significantly diminished the PL017-induced depression of AMPA responses. In addition, when the cells were dialyzed with guanosine 5'-O-(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 magnitude of the KA-induced current in 60% of the tested cells. These results indicate that in acutely isolated rat DH neurons, the activation of mu-opioid receptor inhibits AMPA-activated current through activation of a G-protein. This action may contribute to the regulation of the strength of the primary afferent neurotransmission including nociception.
Kolaj
M
M
Department of Veterinary Physiology and Pharmacology, Iowa State University, Ames 50011, USA. mkolaj@civich.ottawa.on.ca
Randic
M
M
D000595:Amino Acid Sequence; D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D004723:Endorphins / Q000494:pharmacology; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D004745:Enkephalins / Q000494:pharmacology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000378:metabolism; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D008969:Molecular Sequence Data; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D010446:Peptide Fragments; D010455:Peptides / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000187:drug effects / Q000378:metabolism*; D017450:Receptors, Opioid, mu / Q000819:agonists* / Q000037:antagonists & inhibitors*; D013004:Somatostatin; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism*; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology
D000700:Analgesics; C529311:CTAP octapeptide; D004723:Endorphins; D004745:Enkephalins; D018690:Excitatory Amino Acid Agonists; D010446:Peptide Fragments; D010455:Peptides; D018091:Receptors, AMPA; D017450:Receptors, Opioid, mu; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D013004:Somatostatin; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; C044708:morphiceptin, N-Me-Phe(3)-; D019204:GTP-Binding Proteins