S94

AFFINITY OF VARIOUS OPIOID ANTAGONISTS TO RECEPTOR SUBTYPE IN MOUSE VAS DEFERENS

TETSUO OKA, M[DORI KAJIWARA*, KAORI ISHII* AND TERUHIKO MATSUMIYA*, Department of Pharmacology, School of Medicine, Tokai University, Isehara 259- ii, Japan.

The effectiveness of an opioid antagonist against a given agonist was measured by the equilibrium dissociation constant Ke in order to estimate the affinity of an antagonist to receptor subtype. Morphine, ethylketocyclazocine (EKC) or [D-Ala2,D-LeuS]-enkephalin (DADLE) was employed as a representative agonist of the mu, kappa or delta receptor, respectively. The Ke values of both naloxone and nalorphine against morphine were significantly lower than t~ose of either EKC or DADLE. Additionally, their Ke values against DADLE were significantly higher than those against EKC, showing that both naloxone and nalorphine had high, intermediate or low affinities to mu, kappa or delta receptors, respectively. On the other hand, the antagonistic effectiveness of pentazocine was high, intermediate or low against kappa, mu or delta receptors, respectively, although the Ke value against EKC of pentazocine was approximate- ly 25 times higher than that of naloxone. In contrast to peptide antagonists such as ICI-154,129 which had the highest affinity to delta receptors, ten out of eleven non-peptide antagonists employed in the present study bad the lowest affinity to delta receptors. Exceptionally, the Ke value of nalorphine-6- sulfate against EKC was more than ten times higher than that against DADLE. The Ke value against EKC of levallorphan, which was the sole opioid antagonist clinically available in Japan, was significantly lower than that of na]oxone. In contrast to naloxone, the affinity of levallorphan to kappa receptors was similar to or slightly higher than that to mu receptors.

THE EFFECT OF MORPHINE AND (D-ALA,MET)-ENKEPHALINAMIDE ON Ca

DYNAMICS IN THE RAT BRAIN STRIATUM

*i *2 NAKAHIRO*3 KIHACHI SAITO , KENJI ISHII , MASANOBU and Reizo

INOKI I, Department of Pharmacology, iOsaka University, Faculty of

Dentistry, 2Osaka Medical College and 3 Osaka University, Faculty

of Medicine

Two parameters of Ca ++ dynamics in brain preparations (45Ca-

uptake to slices and (3H)-nitrendipine binding to membrane

fractions) were compared in naive and chronic morphine rats.

While morphine didn't have any effect on 45Ca-uptake to striatal

slices in normal Krebs-Ringer solution, it inhibited K+(40mM) -

stimulated 45Ca-uptake to slices. Furthermore, the effect of

morphine was antagonized by naloxone. K+-stimulated 45Ca-uptake

to striatal slices obtained from chronically morphine administered

rats (6mg/kg, twice/day, 7 days) was not inhibited by morphine. In

membrane fractions, (3H)-nitrendipine binding increased by 34 % in

striatum following chronic morphine treatment, whereas no change

was observed in the cortex and hippocampus. The results will be

discussed in relation to the phenomena underlying chronic morphine.