PT - JOURNAL ARTICLE AU - Matthias Schreff AU - Stefan Schulz AU - Manuela Händel AU - Gerburg Keilhoff AU - Holger Braun AU - Gabriela Pereira AU - Marcus Klutzny AU - Harald Schmidt AU - Gerald Wolf AU - Volker Höllt TI - Distribution, Targeting, and Internalization of the sst<sub>4</sub> Somatostatin Receptor in Rat Brain AID - 10.1523/JNEUROSCI.20-10-03785.2000 DP - 2000 May 15 TA - The Journal of Neuroscience PG - 3785--3797 VI - 20 IP - 10 4099 - http://www.jneurosci.org/content/20/10/3785.short 4100 - http://www.jneurosci.org/content/20/10/3785.full SO - J. Neurosci.2000 May 15; 20 AB - 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 sst2A receptor, sst4-immunoreactive dendrites were often closely apposed by somatostatin-14-containing fibers and terminals. However, unlike the sst2A 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 sst4receptor 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.