title: Pattern of Fos expression in the brain induced by selective activation of somatostatin receptor 2 in rats.
abstract: Central activation of somatostatin (sst) receptors by oligosomatostatin analogs inhibits growth hormone and stress-related rise in catecholamine plasma levels while stimulating grooming, feeding behaviors, gastric transit and acid secretion, which can be mimicked by selective sst(2) receptor agonist. To evaluate the pattern of neuronal activation induced by peptide sst receptor agonists, we assessed Fos-expression in rat brain after intracerebroventricular (i.c.v.) injection of a newly developed selective sst(2) agonist compared to the oligosomatostatin ODT8-SST, a pan-sst(1-5) agonist. Ninety min after injection of vehicle (10 microl) or previously established maximal orexigenic dose of peptides (1 microg=1 nmol/rat), brains were assessed for Fos-immunohistochemistry and doublelabeling. Food and water were removed after injection. The sst(2) agonist and ODT8-SST induced a similar Fos distribution pattern except in the arcuate nucleus where only the sst(2) agonist increased Fos. Compared to ODT8-SST, the sst(2) agonist induced higher Fos-expression by 3.7-times in the basolateral amygdaloid nucleus, 1.2-times in the supraoptic nucleus (SON), 1.6-times in the magnocellular paraventricular hypothalamic nucleus (mPVN), 4.1-times in the external lateral parabrachial nucleus, and 2.6-times in both the inferior olivary nucleus and superficial layer of the caudal spinal trigeminal nucleus. Doublelabeling in the hypothalamus showed that ODT8-SST activates 36% of oxytocin, 63% of vasopressin and 79% of sst(2) immunoreactive neurons in the mPVN and 28%, 55% and 25% in the SON, respectively. Selective activation of sst(2) receptor results in a more robust neuronal activation than the pan-sst(1-5) agonist in various brain regions that may have relevance in sst(2) mediated alterations of behavioral, autonomic and endocrine functions.
authors.affiliation: CURE/Digestive Diseases Research Center, Center for Neurobiology of Stress, Digestive Diseases Division, Department of Medicine, David Geffen School of Medicine, UCLA and VA Greater Los Angeles Healthcare System, Los Angeles, California, USA.
authors.forename: Miriam
authors.initials: M
authors.lastname: Goebel
authors.affiliation: CURE/Digestive Diseases Research Center, Center for Neurobiology of Stress, Digestive Diseases Division, Department of Medicine, David Geffen School of Medicine, UCLA and VA Greater Los Angeles Healthcare System, Los Angeles, California, USA.
authors.forename: Andreas
authors.initials: A
authors.lastname: Stengel
authors.affiliation: CURE/Digestive Diseases Research Center, Center for Neurobiology of Stress, Digestive Diseases Division, Department of Medicine, David Geffen School of Medicine, UCLA and VA Greater Los Angeles Healthcare System, Los Angeles, California, USA.
authors.forename: Lixin
authors.initials: L
authors.lastname: Wang
authors.affiliation: Biotechnology Discovery Research, Eli Lilly and Company, Indianapolis, IN, USA.
authors.forename: Tamer
authors.initials: T
authors.lastname: Coskun
authors.affiliation: Biotechnology Discovery Research, Eli Lilly and Company, Indianapolis, IN, USA.
authors.forename: Jorge
authors.initials: J
authors.lastname: Alsina-Fernandez
authors.affiliation: Peptide Biology Laboratories, Salk Institute, La Jolla, CA, USA.
authors.forename: Jean
authors.initials: J
authors.lastname: Rivier
authors.affiliation: CURE/Digestive Diseases Research Center, Center for Neurobiology of Stress, Digestive Diseases Division, Department of Medicine, David Geffen School of Medicine, UCLA and VA Greater Los Angeles Healthcare System, Los Angeles, California, USA. Electronic address: ytache@mednet.ucla.edu.
authors.forename: Yvette
authors.initials: Y
authors.lastname: Taché
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D005786:Gene Expression Regulation; D016762:Genes, fos / Q000502:physiology*; D008297:Male; D010446:Peptide Fragments / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017481:Receptors, Somatostatin / Q000819:agonists / Q000378:metabolism*; D013004:Somatostatin / Q000031:analogs & derivatives / Q000494:pharmacology; D014279:Trigeminal Nucleus, Spinal / Q000187:drug effects / Q000378:metabolism
chemical_list: D010446:Peptide Fragments; D017481:Receptors, Somatostatin; D013004:Somatostatin; C017583:somatostatin, octapeptide-Trp(8)-; C093733:somatostatin receptor 2