title: Selective agonists of somatostatin receptor subtype 1 or 2 injected peripherally induce antihyperalgesic effect in two models of visceral hypersensitivity in mice.
abstract: Somatostatin interacts with five G-protein-coupled receptor (sst1-5). Octreotide, a stable sst2≫3≥5 agonist, exerts a visceral anti-hyperalgesic effect in experimental and clinical studies. Little is known on the receptor subtypes involved. We investigated the influence of the stable sst1-5 agonist, ODT8-SST and selective receptor subtype peptide agonists (3 or 10μg/mouse) injected intraperitoneally (ip) on visceral hypersensitivity in mice induced by repeated noxious colorectal distensions (four sets of three CRD, each at 55mmHg) or corticotropin-releasing factor receptor 1 agonist, cortagine given between two sets of graded CRD (15, 30, 45, and 60mmHg, three times each pressure). The mean visceromotor response (VMR) was assessed using a non-invasive manometry method and values were expressed as percentage of the VMR to the 1st set of CRD baseline or to the 60mmHg CRD, respectively. ODT8-SST (10μg) and the sst2 agonist, S-346-011 (3 and 10μg) prevented mechanically induced visceral hypersensitivity in the three sets of CRD, the sst1 agonist (10μg) blocked only the 2nd set and showed a trend at 3μg while the sst4 agonist had no effect. The selective sst2 antagonist, S-406-028 blocked the sst2 agonist but not the sst1 agonist effect. The sst1 agonist (3 and 10μg) prevented cortagine-induced hypersensitivity to CRD at each pressure while the sst2 agonist at 10μg reduced it. These data indicate that in addition to sst2, the sst1 agonist may provide a novel promising target to alleviate visceral hypersensitivity induced by mechanoreceptor sensitization and more prominently, stress-related visceral nociceptive sensitization.
authors.affiliation: Department of Medicine, CURE: Digestive Diseases Research Center and Oppenheimer Family Center for Neurobiology of Stress, Digestive Diseases Division at the University of California Los Angeles and VA Greater Los Angeles Healthcare System, Los Angeles, CA, USA; Department of Gastroenterology and Hepatology, Wroclaw Medical University, Wroclaw, Poland.
authors.forename: Agata
authors.initials: A
authors.lastname: Mulak
authors.affiliation: Department of Medicine, CURE: Digestive Diseases Research Center and Oppenheimer Family Center for Neurobiology of Stress, Digestive Diseases Division at the University of California Los Angeles and VA Greater Los Angeles Healthcare System, Los Angeles, CA, USA.
authors.forename: Muriel
authors.initials: M
authors.lastname: Larauche
authors.affiliation: Department of Medicine, CURE: Digestive Diseases Research Center and Oppenheimer Family Center for Neurobiology of Stress, Digestive Diseases Division at the University of California Los Angeles and VA Greater Los Angeles Healthcare System, Los Angeles, CA, USA.
authors.forename: Mandy
authors.initials: M
authors.lastname: Biraud
authors.affiliation: Department of Medicine, CURE: Digestive Diseases Research Center and Oppenheimer Family Center for Neurobiology of Stress, Digestive Diseases Division at the University of California Los Angeles and VA Greater Los Angeles Healthcare System, Los Angeles, CA, USA.
authors.forename: Mulugeta
authors.initials: M
authors.lastname: Million
authors.affiliation: The Clayton Foundation Laboratories for Peptide Biology, The Salk Institute, La Jolla, CA, USA.
authors.forename: Jean
authors.initials: J
authors.lastname: Rivier
authors.affiliation: Department of Medicine, CURE: Digestive Diseases Research Center and Oppenheimer Family Center for Neurobiology of Stress, Digestive Diseases Division at the University of California Los Angeles and VA Greater Los Angeles Healthcare System, Los Angeles, CA, USA. Electronic address: ytache@mednet.ucla.edu.
authors.forename: Yvette
authors.initials: Y
authors.lastname: Taché
mesh_terms: D000700:Analgesics / Q000008:administration & dosage*; D000818:Animals; D003346:Corticotropin-Releasing Hormone; D004353:Drug Evaluation, Preclinical; D006930:Hyperalgesia / Q000188:drug therapy*; D043183:Irritable Bowel Syndrome / Q000139:chemically induced / Q000473:pathology*; D008297:Male; D008810:Mice, Inbred C57BL; D010446:Peptide Fragments / Q000008:administration & dosage; D017481:Receptors, Somatostatin / Q000819:agonists*; D011993:Recombinant Fusion Proteins; D013004:Somatostatin / Q000008:administration & dosage / Q000031:analogs & derivatives
chemical_list: D000700:Analgesics; D010446:Peptide Fragments; D017481:Receptors, Somatostatin; D011993:Recombinant Fusion Proteins; C488590:cortagine; C000594154:des-AA(1,4-6,11-13)-(4-nitrophenylalanyl(2)-cysteinyl(3)-tyrosyl(7)-4-aminophenylalanylcarbamoyl(8)-somatostatin-3-(2-naphthyl)-alaninamide; C101130:somatostatin receptor type 1; D013004:Somatostatin; C017583:somatostatin, octapeptide-Trp(8)-; D003346:Corticotropin-Releasing Hormone; C093733:somatostatin receptor 2
keywords: Colorectal distension; Cortagine; Somatostatin agonist; Visceral hypersensitivity