Abstract
The alpha adrenergic agonists [3H]epinephrine and [3H]norepinephrine the antagonist WB-4101 (2-([2',6'-dimethoxy]phenoxyethylamino)methylbenzodioxan), and the ergot alkaloid [3H]dihydroergokryptine bind to membranes from various calf brain regions in a fashion that suggests a selective interaction with alpha adrenergic receptors. Binding sites for [3H]alpha agonists appear to predominate in calf cerebellar cortex, while [3H]WB-4101 sites are more plentiful in the pons. Similar numbers of [3H]agonist and [3H]antagonist sites are found in cerebral cortex. Properties of [3H]dihydroergokryptine binding reflect the relative preponderance of [3H]alpha agonist and [3H]antagonist binding sites in these regions. In cerebral cortex, 300 nM (-)-norepinephrine, which completely inhibits binding of [3H]agonists, and 300 nM indoramin, which affords 100% reduction of [3H]antagonist binding, each decrease the maximal number of [3H]dihydroergokryptine binding sites by about half. These agents in combination abolish binding entirely. In contrast, 300 nM (-)-norepinephrine, but not indoramin, eliminates binding to cerebellar membranes. In pons, the maximal number of [3H]dihydroergokryptine binding sites is reduced 64% and 28%, respectively, by 300 nM indoramin and 300 nM (-)-norepinephrine. Compared with cerebral cortex values, the agonists clonidine and (-)-norepinephrine are more potent [3H]dihydroergokryptine inhibitors in cerebellum and less potent in pons; for the antagonists WB-4101 and indoramin, this relationship is reversed. The apparent Ki values for these agents at [3H]dihydroergokryptine binding sites in cerebellum and pons are similar to values obtained for cortical binding of [3H]agonists and [3H]WB-4101, respectively. These findings support the proposed existence of two discrete populations of alpha adrenergic receptors with respective high affinities for agonists and antagonists and differential regional distribution in the brain, both of which may be labeled by [3H]dihydroergokryptine.
ACKNOWLEDGMENT We thank Pamela Morgan for preparation of the manuscript.
- Copyright © 1978 by Academic Press, Inc.
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