CENTRAL ADMINISTRATION OF 1-ISOPROTERENOL INVIVO INDUCES A PREFERENTIAL REGULATION OF BETA-2-ADRENOCEPTORS IN THE CENTRAL-NERVOUS-SYSTEM OF THE RAT

1-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-mu-g/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 [I-125]iodopindolol ([I-125]IPIN). In sham lesioned rats, infusions of isoproterenol at both doses caused comparable reductions in the density of [I-125]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 [I-125]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 [I-125]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.