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PMID: 10804219 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Distribution, targeting, and internalization of the sst4 somatostatin receptor in rat brain.

The Journal of neuroscience : the official journal of the Society for Neuroscience ·Vol. 20 ·No. 10 ·2000-05-15 ·Pages 3785-97

Schreff M, Schulz S, Händel M, Keilhoff G, Braun H, Pereira G, Klutzny M, Schmidt H, Wolf G, Höllt V

Abstract

Somatostatin mediates its diverse physiological effects through a family of five G-protein-coupled receptors (sst(1)-sst(5)); 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 sst(4) in the rat CNS by raising anti-peptide antisera to the C-terminal tail of sst(4). The specificity of affinity-purified antibodies was demonstrated using immunofluorescent staining of HEK 293 cells stably transfected with an epitope-tagged sst(4) receptor. In Western blotting, the antiserum reacted specifically with a broad band in rat brain, which migrated at approximately 70 kDa before and approximately 50 kDa after enzymatic deglycosylation. sst(4)-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 sst(4)-expressing neurons target this receptor preferentially to their somatodendritic domain. Like the sst(2A) receptor, sst(4)-immunoreactive dendrites were often closely apposed by somatostatin-14-containing fibers and terminals. However, unlike the sst(2A) receptor, sst(4) was not internalized in response to intracerebroventricular administration of somatostatin-14. After percussion trauma of the cortex, neuronal sst(4) receptors progressively declined at the sites of damage. This decline coincided with an induction of sst(4) expression in cells with a glial-like morphology. Together, this study provides the first description of the distribution of immunoreactive sst(4) receptor proteins in rat brain. We show that sst(4) is strictly somatodendritic and most likely functions in a postsynaptic manner. In addition, the sst(4) receptor may have a previously unappreciated function during the neuronal degeneration-regeneration process.

MeSH Terms
Age Factors Amino Acid Sequence Animals Antibody Specificity Brain Injuries/metabolism Cells, Cultured Endocytosis/drug effects,physiology Fluorescent Antibody Technique Humans Kidney/cytology Ligands Male Membrane Proteins Molecular Sequence Data Prosencephalon/chemistry Rabbits Rats Rats, Wistar Receptors, Somatostatin/analysis,genetics,immunology,metabolism Somatostatin/pharmacokinetics Transfection
Chemicals
Ligands Membrane Proteins Receptors, Somatostatin Sstr2 protein, rat somatostatin receptor sst2A somatostatin receptor subtype-4 somatostatin receptor type 1 Somatostatin
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Schreff M
Departments of Pharmacology and Toxicology and Medical Neurobiology, Otto-von-Guericke University, 39120 Magdeburg, Germany.
Schulz S
Händel M
Keilhoff G
Braun H
Pereira G
Klutzny M
Schmidt H
Wolf G
Höllt V
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Article Info
Journal
The Journal of neuroscience : the official journal of the Society for Neuroscience
Abbr.
J Neurosci
ISSN
1529-2401
Published
2000-05-15
Pages
3785-97
Language
English
Region
United States
NLM ID
8102140
PMCID
PMC6772697
Subset
IM
External Links
PubMed source PMC Full Text View journal details
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