RT Journal Article
SR Electronic
T1 Kappa 2 opioid receptors inhibit NMDA receptor-mediated synaptic currents in guinea pig CA3 pyramidal cells
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 5580
OP 5589
DO 10.1523/JNEUROSCI.14-09-05580.1994
VO 14
IS 9
A1 RM Caudle
A1 C Chavkin
A1 R Dubner
YR 1994
UL http://www.jneurosci.org/content/14/9/5580.abstract
AB The role of the endogenous opioid peptide dynorphin (1–17) in regulating NMDA receptor-mediated synaptic currents was examined in guinea pig hippocampus. Schaffer collateral/commissural fiber-evoked NMDA synaptic currents were recorded using whole-cell patch-clamp techniques in CA3 pyramidal cells. Dynorphin was found to have dual effects on NMDA synaptic currents, increasing currents at low concentrations and decreasing currents at high concentrations. Only the inhibitory action of dynorphin was sensitive to naloxone, indicating that this effect was mediated by an opioid receptor. The inhibitory effect was mimicked by bremazocine, but not by U69,593, U50,488, [D- Ala2, N-Me-Phe4, Gly-ol]-enkephalin, or [D-Pen2,5]-enkephalin. Bremazocine's effect was blocked by naloxone, but not by nor- binaltorphimine, cyprodime, or naltrindole. These findings suggest that bremazocine's effect was mediated by the kappa 2 subtype of opioid receptor. In addition, 1 microM naloxone and antisera to dynorphin (1– 17) were found to increase NMDA-mediated synaptic currents. Nor- binaltorphimine, cyprodime, naltrindole, and antisera to met-enkephalin did not increase the NMDA synaptic current. These findings suggest that endogenous dynorphin was acting at kappa 2 receptors to inhibit NMDA receptor-mediated synaptic currents. Overall, these findings indicate that dynorphin is an endogenous agonist for kappa 2 receptors in the CA3 region of the guinea pig hippocampus and that these receptors regulate NMDA receptor function.