S. Regunathan et al., EXPRESSION OF NONADRENERGIC IMIDAZOLINE SITES IN RAT CEREBRAL CORTICAL ASTROCYTES, Journal of neuroscience research, 34(6), 1993, pp. 681-688
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.