Beta-1 adrenergic receptors mediate noradrenergic facilitation of Purkinje cell responses to gamma-aminobutyric acid in cerebellum of rat.

Norepinephrine (NE) may have a major role in modulating the responsiveness of Purkinje cells to the actions of other neurotransmitters in the cerebellum. Specifically, the catecholamine has been shown to enhance inhibitory responses of Purkinje cells to microiontophoretically applied gamma-aminobutyric acid (GABA). This noradrenergic facilitation of GABA has been shown recently to be mediated by beta-adrenergic receptors. The aim of this study was to characterize further the subtype of the beta-receptor involved. The results indicate that practolol, a selective beta-1 blocker, antagonized the NE-induced augmentation of Purkinje cell inhibitory responses to GABA. Zinterol, a selective beta-2 agonist, did not mimic the potentiating effect of NE. Furthermore, the noradrenergic facilitation of GABA-induced inhibition remained unaltered in cerebella subjected to neonatal X-irradiation. This procedure resulted in a decrease in the total cerebellar beta-receptor population yet left unchanged both the number of beta-1 receptors per cerebellum and the radio-resistant Purkinje cells. Together, the data presented here support the hypothesis that the noradrenergic facilitation of GABA-induced inhibition of Purkinje cells is mediated by the activation of cerebellar beta-1 adrenergic receptors located on the Purkinje cells.