Distribution of beta-adrenergic receptors in different cortical and nuclear regions of cat cerebellum, as revealed by binding studies.

Abstract

In addition to mossy fibers and climbing fibers, the cerebellum receives NE-containing fibers originating particularly from the locus coerulus complex. Since the neurotransmitter of the coeruleo-cerebellar afferents acts mainly on Purkinje cells through beta-receptors, experiments were performed in cats to study the regional distribution and properties of the beta-adrenoceptors at corticocerebellar level; moreover, attempts were made to identify also the presence of beta-adrenoceptor binding in the cerebellar nuclei underlying the different zones of the cerebellar cortex. (-)-[3H]Dihydroalprenolol, a very potent beta-adrenergic antagonist, was used to characterize the beta-adrenergic receptors. (-)-[3H]DHA bound specifically to membrane preparations from all the cortical and nuclear zones of the cerebellum. In particular, beta-adrenergic receptors showed a high density and affinity in the cerebellar cortex with no significant difference in the medial with respect to the intermediate-lateral cortical area. The cerebellar nuclei showed a lower density of beta-adrenoceptors with a comparable or slightly lower affinity with respect to the cerebellar cortex. However, no difference was observed between the fastigial nucleus and the interposite-dentate nuclei. Scatchard analysis of saturation data revealed the presence of a single population of high affinity binding sites in all the examined regions, while the Hill plots excluded the presence of cooperative effects among the binding sites. Attempts to differentiate in the cerebellum beta 1- and beta 2-receptors by using agents which act as selective beta 1 and beta 2 ligands indicated that (-)-[3H]DHA specific binding in cerebellar cortex and nuclei affects predominantly the beta 2 subtype of adrenoceptors. A comparison between results obtained from the cerebellar cortex and those obtained from the whole cerebral cortex was also made. The whole cerebral cortex showed a lower density but a higher affinity than the cerebellar cortex. Moreover, inhibition of (-)-[3H]DHA binding by selective beta 1 and beta 2 ligands indicated the prevalence of the beta 1 subtype of adrenoceptors at this level.