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.