Differential supersensitivity of beta-receptor subtypes in rat cortex and cerebellum after central noradrenergic denervation

Inhibition of ³H-dihydroalprenolol binding to rat cortex and cerebellum β-receptors by the selective β₁-antagonist practolol, and the selective β₂-agonist salbutamol, was shallow and biphasic, with log-logit slopes less than 1.0. The relative affinities of these inhibitors suggested that the predominant β-adrenergic receptor population in cortex and cerebellum was β₁ and β₂ respectively. specific lesion of the ascending dorsal norepinephrine bundle, in addition to increasing β-receptor number in the cortex, significantly increased the affinity of practolol, but did not change the affinity of salbutamol, at cortex β receptor sites. Similar lesions decreased cerebellar β-receptor binding and reduced the affinity of salbutamol but not of practolol for those same sites. Iterative computer analysis of the inhibition data showed mixed populations of β₁- and β₂- receptors in both cortex and cerebellum. Dorsal NE bundle lesion doubled the number of cortical β₁-receptors, but did not alter the number of β₂-receptors. In contrast, these lesions induced a selective decrease in cerebellar β₂-receptors. It is concluded that the relevant neuronal β-receptors which are postsynaptic to central NE nerve terminals are β₁ in the cerebral cortex and β₂ in the cerebellum.