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Mouse 5-HT2B receptor-mediated serotonin trophic functions
D S Choi1, O Kellermann, S Richard
1CNRS, INSERM, Institut de Génétique et de Biologie Moléculaire et Cellulaire, Université L. Pasteur de Strasbourg, Illkirch, France.
Abstract:
5-HT2B receptors, in addition to phospholipase C stimulation, are able to trigger activation of the proto-oncogene product p21ras. During mouse embryogenesis, a peak of 5-HT2B receptor expression is detected at the neurulation stage; we localized the 5-HT2B expression in neural crest cells, heart myocardium, and somites. The requirement for functional 5-HT2B receptors shortly after gastrulation, is supported by culture of embryos exposed to 5-HT2B-high affinity antagonist such as ritanserin, which induces morphological defects in the cephalic region, heart and neural tube. Functional 5-HT2B receptors are also expressed during the serotonergic differentiation of the mouse F9 teratocarcinoma-derived clonal cell line 1C11. Upon 2 days of induction by cAMP, 5-HT2B receptors become functional, and on day 4, the appearance of 5-HT2A receptors coincides with the onset of active serotonin transporter by these cells. Active serotonin uptake is modulated by serotonin suggesting autoreceptor functions for 5-HT2B receptors.
Insights
Serotonin 5-HT2B receptors are crucial for mouse embryonic development, particularly during neurulation. Blocking these serotonin receptors causes developmental defects, highlighting their essential role.
Area of Science:
- Developmental Biology
- Neuroscience
- Molecular Biology
Background:
- 5-HT2B receptors activate proto-oncogene product p21ras and phospholipase C.
- Expression of 5-HT2B receptors peaks during mouse neurulation.
- These receptors are found in neural crest cells, heart, and somites.
Purpose of the Study:
- To investigate the role of 5-HT2B receptors during mouse embryogenesis.
- To examine the functional expression of 5-HT2B receptors in a cell line.
- To understand the autoreceptor function of 5-HT2B receptors in serotonin uptake.
Main Methods:
- Localization of 5-HT2B receptor expression in mouse embryos.
- In vitro culture of embryos with 5-HT2B antagonists (e.g., ritanserin).
- Analysis of 5-HT2B and 5-HT2A receptor expression and serotonin transporter activity in 1C11 cells.
Main Results:
- 5-HT2B receptor antagonists induce morphological defects in the cephalic region, heart, and neural tube.
- Functional 5-HT2B receptors appear during the serotonergic differentiation of 1C11 cells.
- Serotonin transporter activity emerges after 5-HT2A receptor appearance and is modulated by serotonin.
Conclusions:
- Functional 5-HT2B receptors are essential for normal mouse embryonic development, particularly neurulation.
- 5-HT2B receptors likely play an autoregulatory role in serotonin uptake.
- The 1C11 cell line provides a model for studying serotonergic differentiation and receptor function.