Susan H. Yamamura

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

Abstract Inhibition of 3 H-dihydroalprenolol binding to rat cortex and cerebellum β-receptors by the selective β 1 -antagonist practolol, and the selective β 2 -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 β 1 and β 2 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 β 1 - and β 2 - receptors in both cortex and cerebellum. Dorsal NE bundle lesion doubled the number of cortical β 1 -receptors, but did not alter the number of β 2 -receptors. In contrast, these lesions induced a selective decrease in cerebellar β 2 -receptors. It is concluded that the relevant neuronal β-receptors which are postsynaptic to central NE nerve terminals are β 1 in the cerebral cortex and β 2 in the cerebellum.

[3H]CL 218,872, a novel triazolopyridazine which labels the benzodiazepine receptor in rat brain

We examined the specific binding of [3H]CL 218,872, a novel triazolopyridazine to benzodiazepine receptors in the rat cerebral cortex. Two binding sites with KD values of about 10-30 nM and 200-600 nM were demonstrated. A number of benzodiazepine anxiolytics inhibited [3H]CL 218,872 binding in a manner which correlates with the potency of these drugs for inhibiting [3H]benzodiazepine binding. Our initial studies show that [3H]CL 218,872 can label the benzodiazepine receptors and may prove to be a useful probe for studying benzodiazepine heterogeneity and regulation.

A novel triazolopyridazine, [3H]CL 218,872 which labels the benzodiazepine receptor in rat brain

Abstract The specific binding of the novel triazolopyridazine, Cl 218,872 was examined in the rat cerebral cortex. Two binding sites with dissociation constants of 10-30nM and 200-400nM were demonstrated. A number of benzodiazepine anxiolytics inhibited 3 H-CL 218, 872 binding in a manner which corelates with the potency of these drugs for inhibiting 3 H-benzodiazepine binding. Our initial characterization show that the triazolopyridazines may discriminate between benzodiazepine receptor subtypes and may prove to be useful probes for examining heterogeneity of the benzodiazepine receptor.