Developmentally regulated serotonin 5-HT2B receptors.
Serotonin (5-hydroxytryptamine, 5-HT) binds to numerous cognate receptors to initiate its biological effects. In this review, we have focused on the 5-HT2B receptor to address how signaling and expression of this receptor is specifically implicated in embryonic development and adult health and disease. Transduction of the 5-HT2B signaling is complex, including phospholipase C and A2 stimulation, cGMP production and a mitogenic signal that integrates the tyrosine kinase-signaling pathway. Furthermore, 5-HT, through the 5-HT2B receptors, has the ability to control serotonergic differentiation of committed neuron-like cells. In addition, 5-HT2B receptors are actively involved in the transient action of 5-HT during embryonic morphogenesis. Our recent data presented the first genetic evidence that 5-HT via 5-HT2B receptors regulates cardiac embryonic development and adult functions and suggested that this receptor subtype may be involved in other physiopathological situations. In particular, 5-HT-dependent molecular mechanisms may be involved in embryonic development and postnatal maturation of the enteric nervous system. Also, the involvement of the 5-HT2B receptor in the vascular growth often observed in hypertension is likely. These probably result from reactivation of developmentally regulated receptors in pathological situations. Finally, embryonic functions of 5-HT2 receptors observed in Drosophila gastrulation suggest evolutionary conserved mechanisms.
Nebigil
C G
CG
Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS, INSERM, Université L. Pasteur de Strasbourg, BP 163-67404 Cedex, Illkirch, France.
Etienne
N
N
Schaerlinger
B
B
Hickel
P
P
Launay
J M
JM
Maroteaux
L
L
D000818:Animals; D002118:Calcium / Q000502:physiology; D002454:Cell Differentiation; D004331:Drosophila melanogaster / Q000196:embryology / Q000235:genetics; D005314:Embryonic and Fetal Development; D017615:Enteric Nervous System / Q000196:embryology / Q000254:growth & development; D019143:Evolution, Molecular; D005318:Fetal Heart / Q000254:growth & development; D005326:Fetal Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D005775:Gastrula; D018507:Gene Expression Regulation, Developmental; D006160:Guanosine Triphosphate / Q000502:physiology; D006801:Humans; D006973:Hypertension / Q000235:genetics / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000502:physiology; D008322:Mammals / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D009024:Morphogenesis; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D011493:Protein Kinase C / Q000502:physiology; D044403:Receptor, Serotonin, 5-HT2B; D011985:Receptors, Serotonin / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D012701:Serotonin / Q000502:physiology; D015398:Signal Transduction; D013045:Species Specificity; D010738:Type C Phospholipases / Q000502:physiology
D005326:Fetal Proteins; D009419:Nerve Tissue Proteins; D044403:Receptor, Serotonin, 5-HT2B; D011985:Receptors, Serotonin; D012701:Serotonin; D006160:Guanosine Triphosphate; D011493:Protein Kinase C; D010738:Type C Phospholipases; D002118:Calcium