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Abstract

Inhibition of norepinephrine release from rat cortex slices by opioids: differences among agonists in sensitivities to antagonists suggest receptor heterogeneity.

K W Kim and B M Cox
Journal of Pharmacology and Experimental Therapeutics December 1993, 267 (3) 1153-1160;
K W Kim
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Abstract

Receptors mediating opiate-induced inhibition of potassium-stimulated release of [3H]norepinephrine (NE) from slices of rat cortex incubated in vitro have been characterized by comparison of the pA2 values of the competitive antagonists, naloxone, D-Pen-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2 (CTOP), nor-binaltorphimine, naltrindole and bremazocine against the agonists, Tyr-D-Ala-MePhe-Gly-ol (DAMGO), Tyr-D-Arg-Phe-Sar (TAPS), [D-Ser2, Leu5]enkephalyl-Thr (DSLET), beta-endorphin [beta-END(1-31)] and ethylketocyclazocine (EKC). There were significant differences among agonists in their sensitivities to each antagonist. The delta receptor selective agonist, DPDPE, and the kappa 1-agonist, U69593, did not inhibit NE release, indicating that delta and kappa 1 receptors are not involved. DAMGO, TAPS and DSLET generally behaved as mu agonists, although TAPS and DSLET were less sensitive to antagonism by CTOP than by DAMGO. TAPS and DSLET showed similar sensitivities to all antagonists, suggesting that they acted through similar receptors, possibly of the mu 1 type. beta-END(1-31) and EKC differed from DAMGO and from each other in their sensitivities to most antagonists. Shifts in agonist concentration-response curves induced by prior treatment of the rats with the noncompetitive antagonists, beta-funaltrexamine and naloxonazine, also suggested that EKC and beta-END(1-31) acted through mechanisms differing from those used by DAMGO, TAPS and DSLET. It is possible that EKC and beta-END(1-31) acted via kappa 2 and/or epsilon receptors. These results suggest that there is heterogeneity in the opioid receptors regulating NE release in rat cortex.

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Journal of Pharmacology and Experimental Therapeutics
Vol. 267, Issue 3
1 Dec 1993
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Abstract

Inhibition of norepinephrine release from rat cortex slices by opioids: differences among agonists in sensitivities to antagonists suggest receptor heterogeneity.

K W Kim and B M Cox
Journal of Pharmacology and Experimental Therapeutics December 1, 1993, 267 (3) 1153-1160;

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Abstract

Inhibition of norepinephrine release from rat cortex slices by opioids: differences among agonists in sensitivities to antagonists suggest receptor heterogeneity.

K W Kim and B M Cox
Journal of Pharmacology and Experimental Therapeutics December 1, 1993, 267 (3) 1153-1160;
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