Differential interaction of guanabenz with receptor binding sites in rat brain and kidney

The α₂-adrenoceptor selective agonist, [³H]guanabenz ([³H]GBZ), labels a unique population of binding sites in whole kidney which are not labeled by [³H]p-aminoclonidine ([³H]PAC). These binding sites are saturable and of high affinity (K(d) = 10-12 nM). [³H]GBZ was not siplaced from these sites by other α₁- or α₂-ligands, suggesting that they are non-adrenergic. This hypothesis is further supported by the insensitivity of renal guanabenz binding to regulation by guanyl nucleotides or to destruction by trypsin. Also, there appears to be no effect of guanabenz on the potency of isoproterenol in competing for β-adrenoceptors in the kidney, which has been previously reported to be sensitive to clonidine. The absence of any effect of guanabenz on isoproterenol displacement of [³H]dihydroalprenolol in kidney suggest there are subtle differences in activation of alpha-receptors by clonidine and guanabenz in the kidney. In the brain, [³H]GBZ labels two binding sites. Part of the binding of [³H]GBZ in the brain is to sites essentially identical to the α₂-adrenoceptors labeled by [³H]PAC. The remainder of the binding resembles the non-adrenergic binding in kidney. The relationship of this unique binding site to the pharmacologic actions of guanabenz is currently not known.