IMIDAZOLINE RECEPTORS AND THEIR ENDOGENOUS LIGANDS

Imidazoline (I) receptors constitute a family of nonadrenergic high-af finity binding sites for clonidine, idazoxan, and allied drugs. One ma jor subclass, the Il receptors, whose subcellular distribution and sig nal transduction mechanisms are uncertain, partly mediates the central hypotensive actions of clonidine-like drugs. The I-2 receptors, anoth er subclass, are mitochondrial, not G protein coupled, and have divers ified functions. Several endogenous ligands for I receptors, collectiv ely termed clinidine-displacing substances (CDSs), have been detected in tissues and serum, but the structure of only one, agmatine (decarbo xylated arginine), is known. Agmatine, widely distributed and bioactiv e, binds, like clonidine, to alpha(2)-adrenergic and I receptors of al l subclasses. The presence of agmatine and its biosynthetic enzyme in synaptosomes and specific neuronal pathways as well as serum suggests that it may be a novel neurotransmitter/hormone. Another CDS that bind s to I receptors and to antibodies to imidazoline drugs has been detec ted, but its structure is unknown.