Central administration of 1-isoproterenol in vivo induces a preferential regulation of β2-adrenoceptors in the central nervous system of the rat

Carla Gambarana, Gregory A. Ordway, Miroslawa Hauptmann, Shanaz Tejani-Butt, Alan Frazer

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

1-Isoproterenol has equal affinity for β1- and β2-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 β2-adrenoceptors. To investigate this phenomenon further, in the present study rats were infused centrally with higher doses of 1-isoproterenol (15 or 45 μg/h). Furthermore, isoproterenol was infused into rats lesioned neonatally with 6-hydroxydopamine (6-OHDA). Subtypes of β-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 β2-adrenoceptors was decreased in a larger number of brain areas than the binding to β1-adrenoceptors and the magnitude of the reduction was greater for β2- than for β2-adrenoceptors. However, isoproterenol at these doses did produce greater effects on the β1-subtype than those found previously with a lower dose. Treatment with 6-OHDA induced significant increases in the binding of [125I]IPIN to both β1- and β2-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 β2-adrenoceptors was reduced to a greater extent that the binding to β1-adrenoceptors. Thus, these studies demonstrate that the non-selective β-adrenergic agonist isoproterenol induces a preferential regulation of β2-adrenoceptors, even at relatively high doses and in norepinephrine-depleted animals.

Original languageEnglish (US)
Pages (from-to)141-148
Number of pages8
JournalBrain Research
Volume555
Issue number1
DOIs
StatePublished - Jul 26 1991
Externally publishedYes

Keywords

  • 6-Hydroxydopamine
  • Antidepressant
  • Down-regulation
  • Isoproterenol
  • Norepinephrine
  • β-Adrenoceptor

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

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