An endogenous clonidine-like substance was isolated from bovine brain and characterized by its chemical and pharmacological properties. The clonidine displacing substance (CDS) is a noncatecholamine, nonpeptide compound. It is devoid of NH2-group, is thermostable, and has a molecular weight of 587.8 ± 2 daltons. CDS binds selectively to α2-adrenergic receptors in rat brain membranes as measured by displacement of specifically bound [3H]clonidine, an α2-adrenergic agonist, and [3H]rauwolscine, an α2-antagonist, with no affinity for α1-adrenergic receptors. In physiological studies CDS mimics clonidine's action as an inhibitor of the electrically induced twitch response and as a partial agonist of the epinephrine-induced platelet aggregation. At the central nervous system CDS antagonizes clonidine action, increases mean arterial pressure when injected into the nucleus reticularis lateralis of rats, and reduces the hypotensive effect upon intracisternal injection. CDS, which interacts at α2-adrenergic receptors and increases mean arterial pressure upon intracerebral injection, may represent a neuroregulator that plays an important role in cardiovascular events.
Address correspondence and reprint requests to Dr. D. Atlas at Dept. of Biological Chemistry, Otto Lowei Center, Hebrew University, Jerusalem, 91904 Israel.
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