Distribution, targeting, and internalization of the sst4 somatostatin receptor in rat brain
| Autor: | Gerald Wolf, Volker Höllt, Gerburg Keilhoff, Stefan Schulz, Marcus Klutzny, Gabriela Pereira, Harald H.H.W. Schmidt, Matthias Schreff, Manuela Händel, Holger Braun |
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| Předmět: |
Male
endocrine system medicine.medical_specialty Molecular Sequence Data Fluorescent Antibody Technique Biology Kidney Ligands Transfection Prosencephalon fluids and secretions Antibody Specificity Internal medicine parasitic diseases medicine Somatostatin receptor 3 Animals Humans Somatostatin receptor 2 Somatostatin receptor 1 Amino Acid Sequence Receptors Somatostatin ARTICLE Rats Wistar Receptor Cells Cultured Somatostatin receptor General Neuroscience fungi Age Factors Membrane Proteins Endocytosis Rats Cell biology Endocrinology medicine.anatomical_structure Somatostatin Cerebral cortex Brain Injuries Forebrain Rabbits hormones hormone substitutes and hormone antagonists |
| Zdroj: | Scopus-Elsevier |
| Popis: | 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 sst4in 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 sst4receptor. 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 sst2Areceptor, sst4-immunoreactive dendrites were often closely apposed by somatostatin-14-containing fibers and terminals. However, unlike the sst2Areceptor, sst4was not internalized in response to intracerebroventricular administration of somatostatin-14. After percussion trauma of the cortex, neuronal sst4receptors progressively declined at the sites of damage. This decline coincided with an induction of sst4expression 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 sst4is strictly somatodendritic and most likely functions in a postsynaptic manner. In addition, the sst4receptor may have a previously unappreciated function during the neuronal degeneration–regeneration process. |
| Databáze: | OpenAIRE |
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