L-Isoproterenol has equal affinity for beta 1- and beta 2-adrenoceptors and is a full agonist at both subtypes. However, when infused in vivo into the rat brain, it has been shown to induce a preferential reduction of central beta 2-adrenoceptors. To investigate this phenomenon further, in the present study rats were infused centrally with higher doses of 1-isoproterenol (15 or 45 micrograms/h). Furthermore, isoproterenol was infused into rats lesioned neonatally with 6-hydroxydopamine (6-OHDA). Subtypes of beta-adrenoceptors were measured by quantitative autoradiography of the binding of [125I]iodopindolol ([125I]IPIN). In sham lesioned rats, infusions of isoproterenol at both doses caused comparable reductions in the density of [125I]IPIN binding sites in many brain regions. The binding to beta 2-adrenoceptors was decreased in a larger number of brain areas than the binding to beta 1-adrenoceptors and the magnitude of the reduction was greater for beta 2- than for beta 1-adrenoceptors. However, isoproterenol at these doses did produce greater effects on the beta 1-subtype than those found previously with a lower dose. Treatment with 6-OHDA induced significant increases in the binding of [125I]IPIN to both beta 1- and beta 2-adrenoceptors in cerebral cortical and hippocampal areas, indicating that endogenous norepinephrine may regulate both subtypes in these regions. Even in the 6-OHDA-lesioned rats, the binding of [125I]IPIN to beta 2-adrenoceptors was reduced to a greater extent that the binding to beta 1-adrenoceptors. Thus, these studies demonstrate that the non-selective beta-adrenergic agonist isoproterenol induces a preferential regulation of beta 2-adrenoceptors, even at relatively high doses and in norepinephrine-depleted animals.

Gambarana, C., Ordway, G.A., Hauptmann, M., Tejani-Butt, S., Frazer, A. (1991). Central administration of 1-isoproterenol in vivo induces a preferential regulation of beta 2-adrenoceptors in the central nervous system of the rat. BRAIN RESEARCH, 555(1), 141-148 [10.1016/0006-8993(91)90870-2].

Central administration of 1-isoproterenol in vivo induces a preferential regulation of beta 2-adrenoceptors in the central nervous system of the rat

Gambarana, C.;
1991-01-01

Abstract

L-Isoproterenol has equal affinity for beta 1- and beta 2-adrenoceptors and is a full agonist at both subtypes. However, when infused in vivo into the rat brain, it has been shown to induce a preferential reduction of central beta 2-adrenoceptors. To investigate this phenomenon further, in the present study rats were infused centrally with higher doses of 1-isoproterenol (15 or 45 micrograms/h). Furthermore, isoproterenol was infused into rats lesioned neonatally with 6-hydroxydopamine (6-OHDA). Subtypes of beta-adrenoceptors were measured by quantitative autoradiography of the binding of [125I]iodopindolol ([125I]IPIN). In sham lesioned rats, infusions of isoproterenol at both doses caused comparable reductions in the density of [125I]IPIN binding sites in many brain regions. The binding to beta 2-adrenoceptors was decreased in a larger number of brain areas than the binding to beta 1-adrenoceptors and the magnitude of the reduction was greater for beta 2- than for beta 1-adrenoceptors. However, isoproterenol at these doses did produce greater effects on the beta 1-subtype than those found previously with a lower dose. Treatment with 6-OHDA induced significant increases in the binding of [125I]IPIN to both beta 1- and beta 2-adrenoceptors in cerebral cortical and hippocampal areas, indicating that endogenous norepinephrine may regulate both subtypes in these regions. Even in the 6-OHDA-lesioned rats, the binding of [125I]IPIN to beta 2-adrenoceptors was reduced to a greater extent that the binding to beta 1-adrenoceptors. Thus, these studies demonstrate that the non-selective beta-adrenergic agonist isoproterenol induces a preferential regulation of beta 2-adrenoceptors, even at relatively high doses and in norepinephrine-depleted animals.
Gambarana, C., Ordway, G.A., Hauptmann, M., Tejani-Butt, S., Frazer, A. (1991). Central administration of 1-isoproterenol in vivo induces a preferential regulation of beta 2-adrenoceptors in the central nervous system of the rat. BRAIN RESEARCH, 555(1), 141-148 [10.1016/0006-8993(91)90870-2].
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11365/34438
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