C P Li1, C Ling, P Biancani, J Behar. 1. Department of Medicine, Rhode Island Hospital, Warren Alpert Medical School of Brown University, Providence, RI, USA.
Abstract
BACKGROUND: Patients with diarrhea and slow transit constipation (STC) have high 5-HT levels. In STC, the high 5-HT levels have been difficult to explain, as 5-HT stimulates peristalsis. Over expression of progesterone (P4) receptors in epithelial and muscle cells of the colon may reconcile this contradiction because P4 decreases SERT and increases 5-HT levels, but their effects are rendered ineffective because of the impaired muscle contraction. AIMS: We examined whether P4 treatment could reduce the stool output in two mouse diarrheal models because of higher 5-HT levels, the SERT knock-out (KO), and the fluoxetine-treated mice. METHODS: Contractility of colon circular muscle strips from wild mice was studied. Fecal water and dry fecal output were measured daily over a 4-day period in wild and SERT-KO mice and in fluoxetine-treated mice treated with IM saline or P4. 5-HT levels were measured using ELISA. KEY RESULTS: Progesterone blocked the spontaneous and stimulated phasic contractions. Fecal water output measured in two consecutive 4-day periods was not different in wild and SERT-KO mice. The fecal output in the SERT-KO mice was higher than in wild mice. P4 treatment reduced the 4-day fecal output in both groups compared with saline treatment. Oral fluoxetine treatment increased 5-HT levels in wild mice and increased the 4-day fecal output compared with oral saline. P4 treatment caused a decrease in the fecal output in both groups. CONCLUSIONS & INFERENCES: Progesterone decreased the contractility of circular muscle strips, and reduced the fecal output in two diarrheal models, the SERT-KO and fluoxetine-treated mice.
BACKGROUND:Patients with diarrhea and slow transit constipation (STC) have high 5-HT levels. In STC, the high 5-HT levels have been difficult to explain, as 5-HT stimulates peristalsis. Over expression of progesterone (P4) receptors in epithelial and muscle cells of the colon may reconcile this contradiction because P4 decreases SERT and increases 5-HT levels, but their effects are rendered ineffective because of the impaired muscle contraction. AIMS: We examined whether P4 treatment could reduce the stool output in two mouse diarrheal models because of higher 5-HT levels, the SERT knock-out (KO), and the fluoxetine-treated mice. METHODS: Contractility of colon circular muscle strips from wild mice was studied. Fecal water and dry fecal output were measured daily over a 4-day period in wild and SERT-KO mice and in fluoxetine-treated mice treated with IM saline or P4. 5-HT levels were measured using ELISA. KEY RESULTS: Progesterone blocked the spontaneous and stimulated phasic contractions. Fecal water output measured in two consecutive 4-day periods was not different in wild and SERT-KO mice. The fecal output in the SERT-KO mice was higher than in wild mice. P4 treatment reduced the 4-day fecal output in both groups compared with saline treatment. Oral fluoxetine treatment increased 5-HT levels in wild mice and increased the 4-day fecal output compared with oral saline. P4 treatment caused a decrease in the fecal output in both groups. CONCLUSIONS & INFERENCES: Progesterone decreased the contractility of circular muscle strips, and reduced the fecal output in two diarrheal models, the SERT-KO and fluoxetine-treated mice.
Authors: Jessica A Slade; Jennifer V Hall; Jennifer Kintner; Regenia Phillips-Campbell; Robert V Schoborg Journal: PLoS One Date: 2016-08-03 Impact factor: 3.240