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The Journal of Neuroscience, May 15, 2000, 20(10):3785-3797

Distribution, Targeting, and Internalization of the sst₄ Somatostatin Receptor in Rat Brain

Matthias Schreff¹, Stefan Schulz¹, Manuela Händel¹, Gerburg Keilhoff², Holger Braun¹, Gabriela Pereira¹, Marcus Klutzny¹, Harald Schmidt¹, Gerald Wolf², and Volker Höllt¹

Departments of ¹ Pharmacology and Toxicology and ² Medical Neurobiology, Otto-von-Guericke University, 39120 Magdeburg, Germany

Somatostatin mediates its diverse physiological effects through a family of five G-protein-coupled receptors (sst₁-sst₅); however, knowledge about the distribution of individual somatostatin receptor proteins in mammalian brain is incomplete. In the present study, we have examined the regional and subcellular distribution of the somatostatin receptor sst₄ in the rat CNS by raising anti-peptide antisera to the C-terminal tail of sst₄. The specificity of affinity-purified antibodies was demonstrated using immunofluorescent staining of HEK 293 cells stably transfected with an epitope-tagged sst₄ receptor. In Western blotting, the antiserum reacted specifically with a broad band in rat brain, which migrated at ~70 kDa before and ~50 kDa after enzymatic deglycosylation. sst₄-Like immunoreactivity was most prominent in many forebrain regions, including the cerebral cortex, hippocampus, striatum, amygdala, and hypothalamus. Analysis at the electron microscopic level revealed that sst₄-expressing neurons target this receptor preferentially to their somatodendritic domain. Like the sst_2A receptor, sst₄-immunoreactive dendrites were often closely apposed by somatostatin-14-containing fibers and terminals. However, unlike the sst_2A receptor, sst₄ was not internalized in response to intracerebroventricular administration of somatostatin-14. After percussion trauma of the cortex, neuronal sst₄ receptors progressively declined at the sites of damage. This decline coincided with an induction of sst₄ expression in cells with a glial-like morphology. Together, this study provides the first description of the distribution of immunoreactive sst₄ receptor proteins in rat brain. We show that sst₄ is strictly somatodendritic and most likely functions in a postsynaptic manner. In addition, the sst₄ receptor may have a previously unappreciated function during the neuronal degeneration-regeneration process.

Key words: somatostatin; somatostatin receptor subtypes; antibodies; immunocytochemistry; internalization; trauma

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Copyright © 2000 Society for Neuroscience  0270-6474/00/20103785-13$05.00/0

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