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 language | English (US) |
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Pages (from-to) | 141-148 |
Number of pages | 8 |
Journal | Brain Research |
Volume | 555 |
Issue number | 1 |
DOIs | |
State | Published - Jul 26 1991 |
Externally published | Yes |
Keywords
- 6-Hydroxydopamine
- Antidepressant
- Down-regulation
- Isoproterenol
- Norepinephrine
- β-Adrenoceptor
ASJC Scopus subject areas
- Clinical Neurology
- Molecular Biology
- General Neuroscience
- Developmental Biology