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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.
AuthorsAgata Mulak, Muriel Larauche, Mandy Biraud, Mulugeta Million, Jean Rivier, Yvette Taché
JournalPeptides (Peptides) Vol. 63 Pg. 71-80 (Jan 2015) ISSN: 1873-5169 [Electronic] United States
PMID25451334 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
CopyrightCopyright © 2014 Elsevier Inc. All rights reserved.
Chemical References
  • Analgesics
  • Peptide Fragments
  • Receptors, Somatostatin
  • Recombinant Fusion Proteins
  • cortagine
  • des-AA(1,4-6,11-13)-(4-nitrophenylalanyl(2)-cysteinyl(3)-tyrosyl(7)-4-aminophenylalanylcarbamoyl(8)-somatostatin-3-(2-naphthyl)-alaninamide
  • somatostatin receptor type 1
  • Somatostatin
  • somatostatin, octapeptide-Trp(8)-
  • Corticotropin-Releasing Hormone
  • somatostatin receptor 2
Topics
  • Analgesics (administration & dosage)
  • Animals
  • Corticotropin-Releasing Hormone
  • Drug Evaluation, Preclinical
  • Hyperalgesia (drug therapy)
  • Irritable Bowel Syndrome (chemically induced, pathology)
  • Male
  • Mice, Inbred C57BL
  • Peptide Fragments (administration & dosage)
  • Receptors, Somatostatin (agonists)
  • Recombinant Fusion Proteins
  • Somatostatin (administration & dosage, analogs & derivatives)

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