A tryptophan-based amino acid neurotransmitter
Serotonin hydrochloride is a monoamine neurotransmitter in the CNS and an endogenous 5-HT receptor agonist. Serotonin hydrochloride is also a catechol O-methyltransferase (COMT) inhibitor with a Ki of 44 μM.
Serotonin hydrochloride is a monoamine neurotransmitter in the CNS and an endogenous 5-HT receptor agonist. Serotonin hydrochloride also inhibits catechol O-methyltransferase (COMT), an enzyme that contributes to modultion the perception of pain, via non-competitive binding to the site bound by catechol substrates with a binding affinity comparable to the binding affinity of catechol itself (Ki=?44 μM). Results show that addition of 100 μM of Serotonin hydrochloride decreases the reaction velocity of COMT[1].
Serotonin hydrochloride produces robust hypersensitivity compare to saline-treated controls (p<0.001)[1]. A significant increase in colonic 5-HT content is observed in IL-13-/- mice receiving Serotonin hydrochloride compare to IL-13-/- receiving vehicle following induction of DSS colitis[2].
参考文献:
[1]. Tsao D, et al. Serotonin-induced hypersensitivity via inhibition of catechol O-methyltransferase activity. Mol Pain. 2012 Apr 13;8:25.
[2]. Shajib MS, et al. Interleukin 13 and serotonin: linking the immune and endocrine systems in murine models of intestinal inflammation. PLoS One. 2013 Aug 28;8(8):e72774.
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Cell experiment: |
For macrophage culture, peritoneal cavity cells are collected from WT and IL-13-/- mice with or without dextran sodium sulfate (DSS) treatment and cultured. Cells are plated at a concentration of 3.0×106 cells per millilitre, and treated with either lipopolysaccharides (LPS); (100 ng/mL) or Serotonin hydrochloride (10-10 M) for 24 hours. The culture supernatant are collected and stored in -80°C until determination of cytokine levels using protein array system[2]. |
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Animal experiment: |
Dextran sodium sulfate (DSS) colitis is induced by orally administering 5% DSS in drinking water for 5 days. In a separate experiment, IL-13-/- mice are injected subcutaneously with 100 mg/kg of Serotonin hydrochloride (5-HTP) twice daily for 8 days beginning 3 days prior to induction of DSS colitis; whereas, the control IL-13-/- mice receive saline as vehicle. Animals are anaesthetized prior to euthanization via cervical dislocation at the conclusion of each experiment or if they reach a predetermined end point (ie, loss of ≥20% body weight and/or significant deterioration of body condition)[2]. |
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参考文献: [1]. Tsao D, et al. Serotonin-induced hypersensitivity via inhibition of catechol O-methyltransferase activity. Mol Pain. 2012 Apr 13;8:25. |
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