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Impaired serotonin transporter function in the small intestine of mice on a high fat diet (1110.6)
Author(s) -
France Marion,
Galligan James,
Swain Greg
Publication year - 2014
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.28.1_supplement.1110.6
Subject(s) - serotonin , serotonin transporter , endocrinology , enterochromaffin cell , medicine , chemistry , jejunum , fluoxetine , serotonin plasma membrane transport proteins , 5 ht receptor , extracellular , small intestine , reuptake inhibitor , motility , receptor , biology , biochemistry , microbiology and biotechnology
Background: Obesity can alter 5‐HT (serotonin) availability in the gut mucosa disrupting motility. 5‐HT availability depends on 5‐HT released from enterochromaffin (EC) cells and by 5‐HT uptake by the serotonin transporter (SERT). We determined if 5‐HT availability was altered in the jejunum of control and high fat fed (HF) obese mice. Methods: 5‐HT mucosal levels were measured using high‐performance liquid chromatography. Amperometry measured 5‐HT availability in real time near the mucosal surface (i.e. near sites of release and uptake). We generated current approach curves in which the electrode distance in relation to the mucosa decreased in a step‐wise fashion. We obtained the slope derived from a linear fit of the ln(current) vs. electrode distance plot. A decrease in 5‐HT uptake caused by the SERT inhibitor fluoxetine (1 μmol L‐1) or cocaine (10 μmol L‐1) was indicated by a decrease in the slope. Results: 5‐HT mucosal levels were not different in HF mice compared to controls. In HF mice, 5‐HT clearance was insensitive to fluoxetine and cocaine compared to controls suggesting SERT function was impaired and other monoamine transporters did not compensate for loss of SERT function. Conclusions: Our data suggests SERT function is impaired in HF mice whereas mucosal 5‐HT levels are unchanged. Impaired SERT function can change GI motility by elevating extracellular 5‐HT and increasing 5‐HT signaling. Grant Funding Source : Supported by R01DK094932