FUNCTIONAL EVIDENCE FOR 2 STEREOCHEMICALLY DIFFERENT ALPHA-2 ADRENOCEPTORS REGULATING CENTRAL NOREPINEPHRINE AND SEROTONIN RELEASE

  • 1 January 1983
    • journal article
    • research article
    • Vol. 224  (3) , 679-684
Abstract
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 KCl. 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 2 enantiomers of mianserin were examined as .alpha.2-adrenoceptor antagonists in the 2 release systems. Only (+)-mianserin was an effective antagonist at the .alpha.2-autoreceptors mediating regulation of norepinephrine release; (-)-mianserin was inactive. Both enantiomers antagonized exogenous norepinephrine at the .alpha.2-adrenoceptors regulating 5-hydroxytryptamine which regulate norepinephrine and serotonin release in the cerebral cortex are evidently located on presynaptic nerve terminals and represent 2 stereochemically different subtypes of .alpha.2-adrenoceptors.