Toll like receptors 2 and 4 exert opposite effects on the contractile response induced by serotonin in mouse colon: Role of serotonin receptors

Microbiota through toll like receptors (TLR) may regulate gastrointestinal motility by activating neuroendocrine mechanisms. We evaluated the influence of TLR2 and TLR4 in spontaneous contractions and serotonin (5-HT)-induced motor response in mouse colon, and the 5-HT receptors involved. Muscle contractility studies to evaluate the intestinal spontaneous motility and the response to 5-HT were performed in the colon from wild type (WT), TLR2^−/−, TLR4^−/−, and TLR2/4 double knockout (DKO) mice. 5-HT receptor mRNA expression was determined by real-time PCR. The amplitude and frequency of the spontaneous contractions of the colon were smaller in TLR4^−/− and TLR2/4DKO respect to WT mice. In WT, TLR2^−/−, and TLR2/4 DKO mice, 5-HT 100 μm evoked a contractile response. The contractile response induced by 5-HT was significantly higher in TLR2^−/− respect to WT mice. In TLR4^−/− mice, 5-HT did not evoke any contractile response. The mRNA expression of 5-HT_2A was increased in TLR2^−/− and TLR2/4 DKO. The 5-HT_2C and 5-HT₄ mRNA expressions were increased in TLR4^−/− and TLR2/4 DKO. The 5-HT_2C mRNA expression was diminished in TLR2^−/- . The 5-HT₃ mRNA expression was increased in TLR2^−/−, TLR4^−/− and TLR2/4 DKO. The 5-HT₇ mRNA expression was diminished in TLR2/4 DKO. In WT, TLR2^−/− and TLR2/4 DKO, 5-HT₂, 5-HT₃, 5-HT₄, and 5-HT₇ receptor antagonists reduced or blocked the contractile response evoked by 5-HT. We postulate that TLR2 and TLR4 modulate the serotonin contractile motor response in mouse colon in an opposite way by modifying the expression of several serotonin receptors.

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