Serotonin and the 5-HT<sub>2B</sub>Receptor in the Development of Enteric Neurons

Fiorica‐Howells, Elena; Maroteaux, Luc; Gershon, Michael D.

doi:10.1523/jneurosci.20-01-00294.2000

Cited by 135 publications

(129 citation statements)

References 72 publications

(70 reference statements)

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“…In the developing gut, a similar pattern of distribution to that of VGF in the developing myenteric plexus has been noted for the serotonin 5-HT 2B receptor (Fiorica-Howells et al 2000) and for cholecystokinin (CCK) (Lay et al 1999). Previous studies demonstrated that VGF mRNA was first detected in migrating neural crest cells and sympathetic and sensory ganglia (Snyder et al 1998), consistent with our localization of VGF in the enteric innervation of the GI tract since the enteric nervous system is derived from neural crest cells that migrate into the gut.…”

Section: Discussionsupporting

confidence: 63%

Expression of VGF mRNA in developing neuroendocrine and endocrine tissues

Snyder¹,

Peng²,

Pintar³

et al. 2003

Journal of Endocrinology

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Analysis of knockout mice suggests that the neurotropininducible secreted polypeptide VGF (non-acronymic) plays an important role in the regulation of energy balance. VGF is synthesized by neurons in the central and peripheral nervous systems (CNS, PNS), as well as in the adult pituitary, adrenal medulla, endocrine cells of the stomach and pancreatic beta cells. Thus VGF, like cholecystokinin, leptin, ghrelin and other peptide hormones that have been shown to regulate feeding and energy expenditure, is synthesized in both the gut and the brain. Although detailed developmental studies of VGF localization in the CNS and PNS have been completed, little is known about the ontogeny of VGF expression in endocrine and neuroendocrine tissues. Here, we report that VGF mRNA is detectable as early as embryonic day 15·5 in the developing rat gastrointestinal and esophageal lumen, pancreas, adrenal, and pituitary, and we further demonstrate that VGF mRNA is synthesized in the gravid rat uterus, together supporting possible functional roles for this polypeptide outside the nervous system and in the enteric plexus.

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Section: Discussionsupporting

confidence: 63%

Expression of VGF mRNA in developing neuroendocrine and endocrine tissues

Snyder¹,

Peng²,

Pintar³

et al. 2003

Journal of Endocrinology

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“…However, this does not exclude the possibility that the higher density of 5-HT cells in the foetal small intestinal mucosa contributes to a higher bioavailability of 5-HT. In this way, it could play a role in the development of the foetal gastrointestinal system as a growth factor and neurotransmitter (Fiorica-Howells et al, 2000;Gershon and Tack, 2007;Gershon, 2013). Ristine and Spear (1984) have suggested an important role for 5-HT in the suckling ritual, based on their experiments in newborn rats, which might explain the high neonatal (day 0) density of 5-HT enterochromaffin cells seen in our study.…”

Section: Discussionmentioning

confidence: 53%

Enteric and serological distribution of serotonin and its precursor tryptophan in perinatal low and normal weight piglets

Willemen

Che

Dewilde

et al. 2014

Animal

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Perinatal mortality is high among small-for-gestational age (SGA) piglets and continues to be an economic burden and threat to animal welfare. As the physiological role of serotonin (5-hydroxytryptamine, 5-HT) in perinatal development and gastrointestinal function in the pig remains unknown, the aim of this study was to assess the enteric distribution of 5-HT cells and to determine 5-HT together with its precursor tryptophan in the serum of perinatal normal and SGA piglets. For this purpose, proximal and distal parts of the small intestine (SI) were processed for immunohistochemical analysis to assess the presence of 5-HT endocrine cells. Serum 5-HT was measured with ELISA, whereas its precursor, that is, the free fraction of tryptophan (FFT) together with albumin-bound tryptophan and total tryptophan, were analysed with HPLC in postnatal piglets. In addition, the morphological growth patterns of the different intestinal tissue layers of both normal and SGA piglets were stereologically analysed. The stereological volume density of 5-HT enteroendocrine cells showed a significant interaction effect between age and region. Indeed, the amount of 5-HT cells in both the proximal and distal part of the SI tended to decrease according to age, with the lowest values detected at day 3 postpartum. No differences could be observed related to BW. Interestingly, the serum concentration of 5-HT was higher in normal piglets compared with SGA piglets. Moreover, the ratio of FFT to total tryptophan was significantly affected by age and BW. Normal piglets had, on average, a lower FFT/total tryptophan ratio compared with SGA piglets. An approximate linear decrease was observed with increasing age. Finally, the immaturity of the intestinal system of the SGA piglets was not reflected in altered volume densities of the different intestinal layers. To conclude, although no BW effect could be detected in the distribution of enteric 5-HT cells, serum 5-HT and the ratio of FFT to total tryptophan ratio showed significant differences between normal piglets and their SGA littermates.Keywords: low birth weight, pig, serotonin, serum, small intestine ImplicationsThe use of hyperprolific sows in the pork industry increases the prevalence of prenatal growth-restricted piglets, characterised by reduced survival rates. Serotonin is prominently present in the gastrointestinal system and regulates feeding behaviour and BW. This study investigated the enteric distribution of serotonin cells and the concentration of this hormone along with its precursor tryptophan in the serum of perinatal SGA and normal littermates. These results -combined with the morphological analysis of the small intestine -will give insight into the endocrine programming and morphological adaptations of the small intestine of SGA piglets.

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“…Previous studies have shown that the 5-HT 2B receptor is also expressed on neurons and smooth muscle cells. 15,16,61 We know that the 5-HT 2B receptor in the rodent gastrointestinal tract is involved in the maturation of neurons 15,29 and in rodent fundus contraction, 62 suggesting a more generalized role for the 5-HT 2B in the control of cell number and function.…”

Section: Discussionmentioning

confidence: 99%

“…26 5-Hydroxytryptamine 1A receptors are also involved in proliferation of T cells and B cells 27 and rat blood lymphocytes. 28 A role for 5-HT 2B receptors in cell differentiation and proliferation has been shown in mouse enteric neurons 29 and hepatocytes. 6 Activation of the 5-HT 2B receptor by 5-HT also induces proliferation of mouse cardiomyocytes 30 and retinal cells in Xenopus, 31,32 indicating a conserved role for 5-HT 2B in regulating cell survival and proliferation in different species.…”

mentioning

confidence: 99%