Role of a Serotonin Precursor in Development of Gut Microvilli

Abstract

Monoamines exert diverse functions in various cells in peripheral organs as well as in the central nervous system. 5-Hydroxy-L-tryptophan (5-HTP)has been simply regarded as a precursor of serotonin , and it is believed that the biological significance of 5-HTP is essentially ascribable to the production of serotonin. Systemic treatment with 5-HTP is often applied to patients with low serotonin levels in the brain. Here we show that endogenous and exogenous 5-HTP but not serotonin induced the development of microvilli in the gut villi epithelium. In contrast, serotonin but not 5-HTP regulated phagocytosis by macrophages. 5-HTP specifically induced actin remodeling and decreased phosphorylation of extracellular signal-regulated kinase (ERK) in the gut, whereas serotonin stimulated actin remodeling and increased ERK phosphorylation in macrophages. Functionally, inhibition of ERK activity promoted the development of microvilli in the gut and ameliorated phagocytosis by macrophages. Thus, 5-HTP and serotonin contribute to distinct cell-type-specific functions via common mediators. Our study might create an opportunity to explore the effects of exogenously applied 5-HTP in humans. The mature small intestinal surface is covered with abundant finger-like villi that project into the luminal space. The apical surface of the mature intestinal epithelium is covered with dense brush border microvilli. The formation of the microvilli is regulated by the organization of individual cell membrane domains and cell:cell junctions via interaction between membrane proteins and actin cytoskeleton.Serotonin [5-hydroxytryptamine (5-HT)] has been implicated in a number of physiological and pathological functions in several peripheral organs and tissues such as liver, platelet, and immune systems.1-6 An enormous proportion of 5-HT is produced in the enterochromaffin cells and is stored in the platelets that release 5-HT in multiple peripheral organs. It has been believed that the released 5-HT essentially exerts its biological effects via 5-HT receptors on various cells in a paracrine manner. There are multiple types of 5-HT receptors that are distributed widely among endocrine, cardiovascular, immune, and gastrointestinal tissues. Receptors for 5-HT fall into one of four distinct families (5-HTR1, 5-HTR2, 5-HTR3, 5-HTR4-7), which are characterized by different signal transduction mechanisms and physiological roles. In the gut, 5-HT plays several physiological roles. For example, 5-HT has been reported to increase the rate at which enterocyte precursors proliferate, and the enhancement of enterocyte proliferation by 5-HT might be mediated by a 5-HT2 receptor. 7The biosynthesis of 5-HT is accomplished through multistep enzyme reactions. Tryptophan hydroxylase-1 (TPH-1) and TPH-2 catalyze the formation of 5-hydroxy-L-tryptophan (5-HTP) from L-tryptophan, the first and ratelimiting step in the biosynthesis of 5-HT. Subsequently, 5-HT is produced from 5-HTP by aromatic L-amino acid decarboxylase (AADC). Despite the frequent use of 5-HTP to t...

Serotonin and the GI tract

“…5-HTP induces development of epithelial microvilli [19]. Reduced serotonin levels promote increased bone mass in a murine model of osteoporosis [20].…”

Structure-Function of Serotonin in Bivalve Molluscs

“…In mammals, there are two isoforms of TPH (TPH1 and TPH2), which are predominantly expressed in the peripheral organs and in the nervous system, respectively. However, TPH1 is the primary form and expresses earlier in neural development [132,133]. Molecular sequence of the gene encoding AADC has also been identified and localized in mammals [134,135].…”

Avaliação dos efeitos de 5-hidroxitriptofano em-hidroxibenzilhidrazine associados a Lactobacillus spp. na morfometria intestinal e imunomarcação de serotonina em frangos de corte desafiados com Salmonella Enteridis

“…Estes achados corroboram com os resultados obtidos por Nakamura et al (2008) que ao administrarem sistemicamente 5HTP e NSD1015, observaram que 5HTP proporcionou aumento na densidade das vilosidades intestinais em testes in vivo realizados em camundongos e in vitro com cultura de linhagens celulares (Caco-2).…”