Alterations in central and renal α-adrenoceptors following chronic clonidine treatment in rats

We have previously shown that there was a significant increase in the cardiac α_1 -adrenoceptors following chronic clonidine treatment in rats (Yamada et al., 1982). In this study we have determined whether chronic treatment (3 weeks) with clonidine (2-3 μmol/kg/day p.o.) would also alter central and renal α-adrenoceptors. Following the clonidine treatment in rats, brain and renal homogenates were prepared and analyzed for ^^3 H-prazosin binding (α_1 -adrenoceptors) and ^^3 H-clonidine binding (α_2 -adrenoceptors). Compared with the control group, specific binding (Bmax value) of ^^3 H-prazosin and ^^3 H-clonidine increased significantly by 23-33 % in renal tissues from the clonidine treated rats (^^3 H-prazosin：13.5±0.2 vs 11.0±0.9, ^^3 H-clonidine：4.89±0.19 vs 3.68±0.30 fmol/mg tissue). The dissociation constant (Kd value) was unchanged. In contrast, chronic treatment with clonidine caused a significant 23 % decrease in specific ^^3 H-clonidine binding in the lower brainstem (Bmax：3.70±0.19 vs 4.83±0.13 fmol/mg tissue) but not in the cerebral cortex, striatum, thalamus, midbrain and cerebellum. These data suggest that following chronic clonidine treatment, α-adrenoceptors in the lower brainstem decrease suggesting central down regulation while the same receptors are up regulated in the periphery.