Analysis of brain adrenergic receptors in dopamine-β-hydroxylase knockout mice

Authors

Jeff D. Sanders, University of Nebraska Medical Center
Patricia Szot, Northwest Network for Mental Illness ResearchFollow
David Weinshenker, Emory University School of MedicineFollow
H. Kevin Happe, Creighton University School of MedicineFollow
David B. Bylund, University of Nebraska Medical CenterFollow
L. Charles Murrin, University of Nebraska Medical CenterFollow

Date of this Version

2006

Document Type

Article

Citation

Brain Research 1109 (2006) 45-53; doi:10.1016/j.brainres.2006.06.033

Abstract

The biosynthesis of norepinephrine occurs through a multi-enzymatic pathway that includes the enzyme dopamine-β-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 (α₁-AR, α₂-AR and β-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 α₁-AR, α₂-AR and β-AR were assayed with [3H]prazosin, [3H]RX21002 and [¹²⁵I]-iodo-pindolol autoradiography, respectively. The α₂-AR agonist high affinity state was examined with [¹²⁵I]-paraiodoclonidine autoradiography and α₂-AR functionality by α₂-AR agonist-stimulated [35S] GTPγS autoradiography. The density of α₁-AR in Dbh−/− mice was similar to Dbh+/− mice in most brain regions, with an up-regulation in the hippocampus. Modest decreases in α₂-AR were found in septum, hippocampus and amygdala, but these were not reflected in α₂-AR functionality. The density of β-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.