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.
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Authors | Agata Mulak, Muriel Larauche, Mandy Biraud, Mulugeta Million, Jean Rivier, Yvette Taché |
Journal | Peptides
(Peptides)
Vol. 63
Pg. 71-80
(Jan 2015)
ISSN: 1873-5169 [Electronic] United States |
PMID | 25451334
(Publication Type: Journal Article, Research Support, N.I.H., Extramural)
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Copyright | Copyright © 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
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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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