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Expression of 5-HT(2A), 5-HT(2B) and 5-HT(2C) receptors in the mouse embryo
1Department of Cell Biology and Anatomy, University of North Carolina School of Medicine, Chapel Hill, CB 7090, NC 27599-7090, USA. unclau@med.unc.edu
Abstract:
Expression patterns of 5-HT(2A), 5-HT(2B) and 5-HT(2C) receptors during mouse embryogenesis were investigated using highly specific monoclonal antibodies. Differential and overlapping spatio-temporal patterns of 5-HT(2A), 5-HT(2B) and 5-HT(2C) receptor immunoreactivity were observed during active phases of morphogenesis of a variety of embryonic tissues, including neuroepithelia of brain and spinal cord, notochord, somites, cranial neural crest, craniofacial mesenchyme and epithelia, heart myocardium and endocardial cushions, tooth germs, whisker follicles, cartilage and striated muscle. The functional significance of these receptors was tested by exposing headfold stage mouse embryos to different subtype-selective 5-HT(2) receptor antagonists for 2 days in whole embryo culture. The most potent was the pan 5-HT(2) receptor antagonist ritanserin, which has high affinity for the 5-HT(2B) receptor. Ritanserin caused 100% malformed embryos at a dose of 1 microM. The 5-HT(2A/2C) receptor antagonist mianserin also caused a significant number of malformed embryos, but only when used at a 10 fold higher dose (10 microM). Ketanserin, which primarily targets 5-HT(2A) receptors, did not cause a significant number of malformed embryos at any dose tested. Together with previous evidence that 5-HT acts as an important morphoregulatory signal during mouse embryogenesis, present evidence for the early and continued expression of functional 5-HT(2) receptors throughout gestation raises the possibility that psychotropic drugs taken during pregnancy could interfere with developmental actions of 5-HT during prenatal development of neural and non-neural tissues.
Insights
Serotonin (5-HT) receptors are expressed throughout mouse development. Blocking these receptors, especially 5-HT(2B), with drugs during pregnancy can cause significant embryonic malformations.
Area of Science:
- Developmental Biology
- Neuroscience
- Pharmacology
Background:
- Serotonin (5-HT) is a key morphoregulatory signal in mouse embryogenesis.
- 5-HT(2A), 5-HT(2B), and 5-HT(2C) receptors are implicated in embryonic development.
- Understanding receptor expression and function is crucial for assessing potential drug impacts.
Purpose of the Study:
- To investigate the spatio-temporal expression patterns of 5-HT(2A), 5-HT(2B), and 5-HT(2C) receptors during mouse embryogenesis.
- To determine the functional significance of these receptors by examining the effects of subtype-selective antagonists on embryonic development.
- To explore the potential risks of psychotropic medications during pregnancy.
Main Methods:
- Utilized highly specific monoclonal antibodies to map receptor expression in embryonic tissues.
- Employed whole embryo culture to expose headfold stage mouse embryos to 5-HT(2) receptor antagonists.
- Assessed malformation rates in response to varying doses of ritanserin, mianserin, and ketanserin.
Main Results:
- Differential and overlapping expression of 5-HT(2A), 5-HT(2B), and 5-HT(2C) receptors was observed in diverse embryonic tissues.
- The pan 5-HT(2) antagonist ritanserin (high affinity for 5-HT(2B)) caused 100% malformations at 1 microM.
- The 5-HT(2A/2C) antagonist mianserin caused significant malformations at 10 microM, while the 5-HT(2A) antagonist ketanserin had no significant effect.
Conclusions:
- Functional 5-HT(2) receptors are expressed early and continuously during mouse gestation.
- Disruption of these receptors by antagonists can lead to severe developmental abnormalities.
- Prenatal exposure to certain psychotropic drugs may interfere with serotonin's developmental signaling, impacting both neural and non-neural tissues.