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Serotonin Type 3 Receptor B Subunit (5‐HT 3B R) and Corticotropin‐Releasing Hormone (CRH) Expression in the Serotonin Transporter Knockout (SERT KO) Rat Model of Visceral Hypersensitivity
Author(s) -
Mecca Andrew,
ElAyache Nadine,
Galligan James
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.1021.1
Subject(s) - serotonin transporter , medicine , endocrinology , corticotropin releasing hormone , irritable bowel syndrome , serotonin , visceral pain , serotonergic , hormone , receptor , nociception
Background Visceral hypersensitivity is a chronic abdominal pain symptom present in functional gastrointestinal disorders such as irritable bowel syndrome (IBS). IBS is a global health issue, and is more prevalent in females than in males suggesting a potential role of female sex hormones in its pathogenesis. Some drug treatments for IBS target the ionotropic serotonin type 3 receptor (5‐HT 3 R), but these drugs have limited clinical benefit and can be associated with serious side effects. Therefore, a deeper understanding of the pathophysiology of visceral hypersensitivity is crucial for the development of more effective treatments. Environmental stress and altered serotonergic signaling may influence the severity of visceral hypersensitivity in IBS patients. Corticotropin‐releasing hormone (CRH) is an important mediator of the neuroendocrine stress response, but its role in IBS needs to be further studied. Aim/Methods We studied the expression of CRH and the B‐subunit of the 5‐HT 3B R in the lumbar spinal cord, colon and lumbar dorsal root ganglia (DRG), in a serotonin‐transporter knockout (SERT KO) rat model of visceral hypersensitivity using immunohistochemistry and real‐time quantitative PCR. Results Female SERT KO rats have higher proportion of CRH+ neurons in DRG than male SERT KO rats (P < 0.01), and CRH was most strongly expressed by small‐diameter nerve cell bodies that are likely to be involved in the pain pathway. There was no difference in the distribution of 5‐HT 3B Rs in the dorsal spinal cord or colon between SERT KO and WT animals. Similarly, there was no difference in CRH+ neurons in the spinal cord, and no difference in CRH expression in the colon between SERT KO and WT. However, we found a 10‐fold and 6‐fold increase in CRH mRNA expression in female and male SERT KO rats, respectively, compared with wildtype controls (P < 0.05). Lastly, preliminary data show that there is no difference in the mRNA transcript for the 5‐HT 3B R in DRG between SERT KO and WT rats. Conclusions We found a novel sex‐specific increase in CRH expression in female SERT KO animals at the level of primary afferent neurons at the protein and mRNA levels. We found no difference in the distribution of the 5‐HT 3B R between SERT KO and WT in the colon, DRG and spinal cord. Our results support our hypothesis that environmental stress mediated by CRH may influence visceral hypersensitivity in IBS.