EXPRESSION OF NONADRENERGIC IMIDAZOLINE SITES IN RAT CEREBRAL CORTICAL ASTROCYTES

Clonidine and related imidazoline agents, beside binding to alpha2-adr energic receptors, have been shown to bind to a non-adrenergic site (i midazoline sites) in brain and peripheral tissues. However, which cell types in brain, namely neurons or glia, express this binding site and the cellular effects of activation of this site are not known. We inv estigated the cellular localization of imidazoline binding sites in cu ltured rat cortical astrocytes and neurons. Membranes prepared from cu ltured astrocytes showed specific, high affinity binding (KD: 4 nM) fo r H-3-idazoxan with about tenfold higher number of binding sites than alpha2-adrenergic sites (B(max): 220 vs. 20 fmol/mg protein). Displace ment studies exhibited the rank order of potency: cirazoline > idazoxa n > amiloride > clonidine >>> epinephrine = ruawolscine defining this site as I-2a subtype of imidazoline binding sites. Moreover, the bindi ng was inhibited by K+ but not by Na+, another characteristic of imida zoline binding sites. In contrast, membranes prepared from cultured ne urons showed fewer binding sites for H-3-idazoxan that were completely displaced by adrenergic agents. Incubation of astrocytes with idazoxa n, but not rauwolscine, resulted in a concentration-dependent increase in the levels of mRNA for the astrocyte specific molecule glial fibri llary acidic protein. We conclude that (a) the non-adrenergic imidazol ine binding sites are expressed in astrocytes but not in neurons in ra t cerebral cortex and (b) these ''receptors'' may influence astrocyte physiology by regulating the levels of GFAP.