Analysis of brain adrenergic receptors in dopamine-beta-hydroxylase knockout mice.
Brain Res
; 1109(1): 45-53, 2006 Sep 13.
Article
em En
| MEDLINE
| ID: mdl-16854392
ABSTRACT
The biosynthesis of norepinephrine occurs through a multi-enzymatic pathway that includes the enzyme dopamine-beta-hydroxylase (DBH). Mice with a homozygous deletion of DBH (Dbh-/-) have a selective and complete absence of norepinephrine. The purpose of this study was to assess the expression of alpha-1, alpha-2 and beta adrenergic receptors (alpha1-AR, alpha2-AR and beta-AR) in the postnatal absence of norepinephrine by comparing noradrenergic receptors in Dbh-/- mice with those in Dbh heterozygotes (Dbh+/-), which have normal levels of norepinephrine throughout life. The densities of alpha1-AR, alpha2-AR and beta-AR were assayed with [3H]prazosin, [3H]RX21002 and [125I]-iodo-pindolol autoradiography, respectively. The alpha2-AR agonist high affinity state was examined with [125I]-para-iodoclonidine autoradiography and alpha2-AR functionality by alpha2-AR agonist-stimulated [35S]GTPgammaS autoradiography. The density of alpha1-AR in Dbh-/- mice was similar to Dbh+/- mice in most brain regions, with an up-regulation in the hippocampus. Modest decreases in alpha2-AR were found in septum, hippocampus and amygdala, but these were not reflected in alpha2-AR functionality. The density of beta-AR was up-regulated to varying degrees in many brain regions of Dbh-/- mice compared to the heterozygotes. These findings indicate that regulation of noradrenergic receptors by endogenous norepinephrine depends on receptor type and neuroanatomical region.
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Base de dados:
MEDLINE
Assunto principal:
Encéfalo
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Receptores Adrenérgicos alfa 2
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Receptores Adrenérgicos alfa 1
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Dopamina beta-Hidroxilase
Idioma:
En
Ano de publicação:
2006
Tipo de documento:
Article