Central administration of 1-isoproterenol in vivo 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 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
C
Dept. of Psychiatry, University of Pennsylvania, Philadelphia.
Ordway
G A
GA
Hauptmann
M
M
Tejani-Butt
S
S
Frazer
A
A
D000818:Animals; D001345:Autoradiography; D002490:Central Nervous System / Q000187:drug effects*; D007276:Injections, Intraventricular; D020120:Iodocyanopindolol; D007545:Isoproterenol / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D009638:Norepinephrine / Q000502:physiology; D016627:Oxidopamine / Q000494:pharmacology; D010869:Pindolol / Q000031:analogs & derivatives; D051381:Rats; D011919:Rats, Inbred Strains; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*
D011943:Receptors, Adrenergic, beta; D020120:Iodocyanopindolol; D016627:Oxidopamine; D010869:Pindolol; D007545:Isoproterenol; D009638:Norepinephrine