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Volume 16, Number 14, Issue of July 15, 1996 pp. 4468-4478
Copyright ©1996 Society for Neuroscience

Localization of the Somatostatin Receptor SST_2A in Rat Brain Using a Specific Anti-Peptide Antibody

Received Feb. 5, 1996; revised April 22, 1996; accepted April 24, 1996.

Pascal Dournaud¹, Yi Z. Gu³, Agnes Schonbrunn³, Jean Mazella¹, Gloria S. Tannenbaum^{1, 2}, and Alain Beaudet¹

Departments of ¹ Neurology and Neurosurgery and ² Pediatrics, McGill University, Montréal, Québec, Canada H3A 2B4, and ³ Department of Pharmacology, University of Texas, Houston Medical School, Houston, Texas 77225

Biological actions of somatostatin are exerted via a family of receptors, for which five genes recently have been cloned. However, none of these receptor proteins has been visualized yet in the brain. In the present study, the regional and cellular distribution of the somatostatin sst_2A receptor was investigated via immunocytochemistry in the rat central nervous system by using an antibody generated against a unique sequence of the receptor protein. Specificity of the antiserum was demonstrated by immunoblot and immunocytochemistry on rat brain membranes and/or on cells transfected with cDNA encoding the different sst receptor subtypes. In rat brain sections, sst_2A receptor immunoreactivity was concentrated either in perikarya and dendrites or in axon terminals distributed throughout the neuropil. Somatodendritic labeling was most prominent in the olfactory tubercle, layers II-III of the cerebral cortex, nucleus accumbens, pyramidal cells of CA1-CA2 subfields of the hippocampus, central and cortical amygdaloid nuclei, and locus coeruleus. Labeled terminals were detected mainly in the endopiriform nucleus, deep layers of the cortex, claustrum, substantia innominata, subiculum, basolateral amygdala, medial habenula, and periaqueductal gray. Electron microscopy confirmed the association of sst_2A receptors with perikarya and dendrites in the former regions and with axon terminals in the latter. These results provide the first characterization of the cellular distribution of a somatostatin receptor in mammalian brain. The widespread distribution of the sst_2A receptor in cerebral cortex and limbic structures suggests that it is involved in the transduction of both pre- and postsynaptic effects of somatostatin on cognition, learning, and memory.

Key words: immunohistochemistry; somatostatin; receptor; transfected cells; electron microscopy; central nervous system

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