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Abstract

Differential sensitivity of recombinant N-methyl-D-aspartate receptor subunits to inhibition by dynorphin.

U Brauneis, M Oz, R W Peoples, F F Weight and L Zhang
Journal of Pharmacology and Experimental Therapeutics December 1996, 279 (3) 1063-1068;
U Brauneis
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M Oz
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R W Peoples
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F F Weight
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L Zhang
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Abstract

Dynorphin is an endogenous ligand for kappa-opioid receptors. We investigated the effect of dynorphin 1-13 on different heteromeric subunits of recombinant mouse N-methyl-D-aspartate (NMDA) receptors expressed in Xenopus oocytes by using voltage-clamp recording methods. Dynorphin inhibited the NMDA-activated currents of all heteromeric NMDA receptor subunits tested. The different NMDA receptor subunits, however, exhibited a differential sensitivity to dynorphin. For the epsilon-1/zeta-1 subunit combination the EC50 was 19 microM; the other NMDA receptor subunit combinations were less sensitive to dynorphin and had the following order of sensitivity: epsilon-2/zeta-1 > epsilon-4/zeta-1 > epsilon-3/zeta-1. Inhibition of NMDA-activated currents by dynorphin was not competitive with NMDA, and was voltage-independent. NMDA-activated currents were not affected by the synthetic kappa-opioid receptor agonist U50488 ¿trans-3, 4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)-cyclohexyl]benzene-acetamide¿, the specific kappa-opioid receptor antagonist nor-binaltorphimine1 or the nonspecific opioid receptor antagonist naloxone. In addition, nor-binaltorphimine1 or naloxone did not attenuate dynorphin inhibition of NMDA-activated current. The observations suggest that dynorphin inhibition of NMDA receptor function is mediated by an interaction of dynorphin with NMDA receptors, rather than an action involving kappa-opioid receptors. The data also show that different heteromeric NMDA receptor subunits exhibit a differential sensitivity to dynorphin.

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Journal of Pharmacology and Experimental Therapeutics
Vol. 279, Issue 3
1 Dec 1996
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Abstract

Differential sensitivity of recombinant N-methyl-D-aspartate receptor subunits to inhibition by dynorphin.

U Brauneis, M Oz, R W Peoples, F F Weight and L Zhang
Journal of Pharmacology and Experimental Therapeutics December 1, 1996, 279 (3) 1063-1068;

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Abstract

Differential sensitivity of recombinant N-methyl-D-aspartate receptor subunits to inhibition by dynorphin.

U Brauneis, M Oz, R W Peoples, F F Weight and L Zhang
Journal of Pharmacology and Experimental Therapeutics December 1, 1996, 279 (3) 1063-1068;
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