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Functional evidence for two stereochemically different alpha-2 adrenoceptors regulating central norepinephrine and serotonin release

M Raiteri, G Maura and P Versace

The effects of norepinephrine and of various alpha adrenoceptor antagonists on the depolarization-evoked release of norepinephrine and 5-hydroxytryptamine were studied in nerve terminals isolated from rat cerebral cortex, preincubated with the radioactive amines and exposed during superfusion to 15 mM KCI. Exogenous norepinephrine inhibited in a concentration-dependent way both the release of norepinephrine and that of serotonin. The inhibitory effect of norepinephrine was antagonized by yohimbine and mianserin, but not by prazosin, indicating the involvement of alpha-2 adrenoceptors. The two enantiomers of mianserin were examined as alpha-2 adrenoceptor antagonists in the two release systems. Only (+)-mianserin was an effective antagonist at the alpha-2 autoreceptors mediating regulation of norepinephrine release; (- )-mianserin was inactive. In contrast, both enantiomers antagonized exogenous norepinephrine at the alpha-2 adrenoceptors regulating 5- hydroxytryptamine release. It can be concluded that the alpha-2 adrenoceptors which regulate, respectively, norepinephrine and serotonin release in the cerebral cortex are located on presynaptic nerve terminals and represent two stereochemically different subtypes of alpha-2 adrenoceptors.

Volume 224, Issue 3, pp. 679-684, 03/01/1983
Copyright © 1983 by American Society for Pharmacology and Experimental Therapeutics




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Copyright © 1983 by the American Society for Pharmacology and Experimental Therapeutics.