Peripheral Serotonin Synthesis as a New Drug Target

Matthes, Susann; Bäder, Michael

doi:10.1016/j.tips.2018.03.004

Cited by 78 publications

(76 citation statements)

References 127 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Since 2003 (classification of TPH isoform), both academia and the pharmaceutical industry have worked on TPH 1 inhibitors as pharmacological targets, in order to decrease peripheral serotonin synthesis. Benefits on multiple diseases are expected: carcinoid syndrome, pulmonary arterial hypertension, obesity, diabetes, and gastrointestinal disorders . However, the results of our study suggest that peripheral serotonin is involved in MDE pathophysiology.…”

Section: Discussionmentioning

confidence: 51%

“…It has been proposed that this decrease in circulating serotonin in patients treated with AD is the result of a decrease in serotonin platelet content due to inhibition of serotonin reuptake by AD treatment. Indeed, when serotonin is not taken up by platelets, which – along with the gut – represent the major peripheral reservoir, it is degraded by the intestinal, liver, and lung cells . Of note, this mechanism induced by serotonin reuptake inhibition in platelets is present only in the blood but not in brain cells.…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, the observed decrease in peripheral serotonin levels in MDE patients could be the result of either a low rate of synthesis and/or a high turnover. Peripheral serotonin synthesis depends on availability of tryptophan and two enzymatic conversions . First, tryptophan hydroxylase 1 catalyzes the conversion of tryptophan to 5‐hydroxytryptophan.…”

mentioning

confidence: 99%

“…First, tryptophan hydroxylase 1 catalyzes the conversion of tryptophan to 5‐hydroxytryptophan. Second, 5‐hydroxytryptophan is converted into serotonin by aromatic amino acid decarboxylase enzymes . In the case of a high turnover rate, an increase in metabolite levels should be observed.…”

mentioning

confidence: 99%

“…Peripheral serotonin synthesis depends on availability of tryptophan and two enzymatic conversions. 16 First, tryptophan hydroxylase 1 catalyzes the conversion of tryptophan to 5-hydroxytryptophan. Second, 5-hydroxytryptophan is converted into serotonin by aromatic amino acid decarboxylase enzymes.…”

mentioning

confidence: 99%

See 4 more Smart Citations

Peripheral tryptophan, serotonin, kynurenine, and their metabolites in major depression: A case–control study

Colle

Masson

Verstuyft

et al. 2019

Psychiatry Clin Neurosci

View full text Add to dashboard Cite

Aim Tryptophan is the sole precursor of both peripherally and centrally produced serotonin and kynurenine. In depressed patients, tryptophan, serotonin, kynurenine, and their metabolite levels remain unclear. Therefore, peripheral tryptophan and metabolites of serotonin and kynurenine were investigated extensively in 173 patients suffering from a current major depressive episode (MDE) and compared to 214 healthy controls (HC). Methods Fasting plasma levels of 11 peripheral metabolites were quantified: tryptophan, serotonin pathway (serotonin, its precursor 5‐hydroxytryptophan and its metabolite 5‐hydroxyindoleacetic acid), and kynurenine pathway (kynurenine and six of its metabolites: anthranilic acid, kynurenic acid, nicotinamide, picolinic acid, xanthurenic acid, and 3‐hydroxyanthranilic acid). Results Sixty (34.7%) patients were antidepressant‐drug free. Tryptophan levels did not differ between MDE patients and HC. Serotonin and its precursor (5‐hydroxytryptophan) levels were lower in MDE patients than in HC, whereas, its metabolite (5‐hydroxyindoleacetic acid) levels were within the standard range. Kynurenine and four of its metabolites (kynurenic acid, nicotinamide, picolinic acid, and xanthurenic acid) were lower in MDE patients. Conclusion Whilst the results of this study demonstrate an association between the metabolites studied and depression, conclusions about causality cannot be made. This study uses the largest ever sample of MDE patients, with an extensive assessment of peripheral tryptophan metabolism in plasma. These findings provide new insights into the peripheral signature of MDE. The reasons for these changes should be further investigated. These results might suggest new antidepressant therapeutic strategies.

show abstract

Section: Discussionmentioning

confidence: 51%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations

Peripheral tryptophan, serotonin, kynurenine, and their metabolites in major depression: A case–control study

Colle

Masson

Verstuyft

et al. 2019

Psychiatry Clin Neurosci

View full text Add to dashboard Cite

show abstract

Serotonin and Pulmonary Hypertension; Sex and Drugs and ROCK and Rho

MacLean¹,

Fanburg²,

Hill³

et al. 2022

Comprehensive Physiology

View full text Add to dashboard Cite

An Insight into the Roles of Dietary Tryptophan and Its Metabolites in Intestinal Inflammation and Inflammatory Bowel Disease

Zhang

Zabed

et al. 2021

Molecular Nutrition Food Res

View full text Add to dashboard Cite

Inflammatory bowel disease (IBD) is complex, chronic, and relapsing gastrointestinal inflammatory disorders, which includes mainly two conditions, namely ulcerative colitis (UC) and Crohn's disease (CD). Development of IBD in any individual is closely related to his/her autoimmune regulation, gene‐microbiota interactions, and dietary factors. Dietary tryptophan (Trp) is an essential amino acid for intestinal mucosal cells, and it is associated with the intestinal inflammation, epithelial barrier, and energy homeostasis of the host. According to recent studies, Trp and its three major metabolic pathways, namely kynurenine (KYN) pathway, indole pathway, and 5‐hydroxytryptamine (5‐HT) pathway, have vital roles in the regulation of intestinal inflammation by acting directly or indirectly on the pro/anti‐inflammatory cytokines, functions of various immune cells, as well as the intestinal microbial composition and homeostasis. In this review, recent advances in Trp‐ and its metabolites‐associated intestinal inflammation are summarized. It further discusses the complex mechanisms and interrelationships of the three major metabolic pathways of Trp in regulating inflammation, which could elucidate the value of dietary Trp to be used as a nutrient for IBD patients.

show abstract

Peripheral Serotonin Synthesis as a New Drug Target

Cited by 78 publications

References 127 publications

Peripheral tryptophan, serotonin, kynurenine, and their metabolites in major depression: A case–control study

Peripheral tryptophan, serotonin, kynurenine, and their metabolites in major depression: A case–control study

Serotonin and Pulmonary Hypertension; Sex and Drugs and ROCK and Rho

An Insight into the Roles of Dietary Tryptophan and Its Metabolites in Intestinal Inflammation and Inflammatory Bowel Disease

Contact Info

Product

Resources

About