Selective survival of ß 1-adenergic receptors in rat cerebellum following neonatal X-irradiation

Abstract

Although beta 2-adrenergic receptors predominate in adult rat cerebellum, a small number of beta 1-receptors are also present. To investigate the cellular localization of beta 1- and beta 2-adrenergic receptors, the effects of intermittent neonatal X-irradiation focused on the cerebellum were determined on the densities of the two subtypes of beta-adrenergic receptor. This treatment destroys the late-maturing cerebellar interneurons including the granule, basket and stellate cells. A 60--70% loss of cerebellar mass was observed in 2-, 6- and 12-week-old animals. The large early-maturing Purkinje cells are resistant to the effects of X-irradiation. The total number of beta-adrenergic receptors per cerebellum, measured by Scatchard analysis of saturation isotherms of specific [125I]iodohydroxybenzylpindolol (IHYP) binding, was reduced by 70--80% in 2-, 6- and 12-week-old animals. The relative proportion of beta 1- and beta 2-receptors was determined by analyzing the inhibition of specific IHYP binding by the beta 1 selective antagonist practolol. The total number of beta 2-adrenergic receptors per cerebellum was reduced by 81--83% in 6- and 12-week-old X-irradiated rats. However, the number of beta 1-adrenergic receptors per cerebellum in 6- and 12-week-old X-irradiated rats was not significantly different from that in control animals. The results suggest that beta 2 receptors in the rat cerebellum are primarily associated with the small interneurons destroyed by neonatal X-irradiation. The beta 1 receptors may be located on a cell population which is unaffected by this treatment, possibly on cerebellar Purkinje cells.