Expression of 5-HT(2A), 5-HT(2B) and 5-HT(2C) receptors in the mouse embryo.
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.
Lauder
J M
JM
Department of Cell Biology and Anatomy, University of North Carolina School of Medicine, Chapel Hill, CB 7090, NC 27599-7090, USA. unclau@med.unc.edu
Wilkie
M B
MB
Wu
C
C
Singh
S
S
D000327:Adsorption; D000818:Animals; D000911:Antibodies, Monoclonal; D001921:Brain / Q000196:embryology*; D001923:Brain Chemistry / Q000502:physiology; D019465:Craniofacial Abnormalities / Q000139:chemically induced / Q000473:pathology; D018604:Epitope Mapping; D005260:Female; D005982:Glutathione Transferase / Q000737:chemistry; D007150:Immunohistochemistry; D051379:Mice; D009432:Neural Crest / Q000187:drug effects / Q000196:embryology; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry; D011247:Pregnancy; D044402:Receptor, Serotonin, 5-HT2A; D044403:Receptor, Serotonin, 5-HT2B; D044405:Receptor, Serotonin, 5-HT2C; D011985:Receptors, Serotonin / Q000096:biosynthesis*; D011993:Recombinant Fusion Proteins / Q000737:chemistry; D012702:Serotonin Antagonists / Q000633:toxicity; D013723:Teratogens / Q000633:toxicity
D000911:Antibodies, Monoclonal; D010455:Peptides; D044402:Receptor, Serotonin, 5-HT2A; D044403:Receptor, Serotonin, 5-HT2B; D044405:Receptor, Serotonin, 5-HT2C; D011985:Receptors, Serotonin; D011993:Recombinant Fusion Proteins; D012702:Serotonin Antagonists; D013723:Teratogens; D005982:Glutathione Transferase