Inhibition of K+-stimulated [3H]dopamine and [14C]acetylcholine Release by the Putative Dopamine Autoreceptor Agonist, B-HT 920

Overview

Journal Naunyn Schmiedebergs Arch Pharmacol

Specialty Pharmacology

Date 1986 Dec 1

PMID 2434870

Citations 2

Authors

C J Schmidt

A Lobur

W Lovenberg

Affiliations

Soon will be listed here.

Abstract

The inhibition of K+-stimulated [3H]dopamine and [14C]acetylcholine release from preloaded rat striatal slices was used to examine the presynaptic selectivity of the putative dopamine autoreceptor agonist, B-HT 920. In the micromolar range, B-HT 920 caused a concentration-dependent inhibition of the release of both labeled neurotransmitters as evoked by 20 mM K+. The effect of B-HT 920 on both [3H]dopamine and [14C]acetylcholine release was completely blocked by (+) butaclamol but not by (-) butaclamol. Sulpiride, a selective D2 antagonist, similarly blocked the inhibitory effect of B-HT 920 on the release of both labeled neurotransmitters indicating both responses were mediated by D2 receptors. (+) Butaclamol alone elevated stimulated [3H]dopamine release suggesting a significant amount of autoreceptor occupancy by endogenously released dopamine. Experiments with tolazoline and the alpha 2 agonist, B-HT 933, did not suggest any involvement of alpha-adrenoceptor activity in the inhibitory effects of B-HT 920 on the release of either transmitter. Inhibition of release was a selective effect of B-HT 920 as the drug was without effect on the K+-stimulated release of [3H]serotonin. The results indicate that in vitro B-HT 920 is active of both pre- and postsynaptic dopamine receptors in contrast to the pattern of effects observed after its in vivo administration.

Citing Articles

Evidence for postsynaptic dopamine agonist effects of B-HT 920 in the presence of the dopamine D-1 agonist SKF 38393.

Meltzer L, WILEY J, Williams A, Heffner T Psychopharmacology (Berl). 1988; 95(3):329-32.

PMID: 2901126 DOI: 10.1007/BF00181942.

B-HT 920 activates dopamine D2 receptors coupled to inhibition of adenylate cyclase activity.

Onali P, Olianas M J Neural Transm Gen Sect. 1992; 88(2):95-104.

PMID: 1352980 DOI: 10.1007/BF01244815.

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