title: WAY-100635, an antagonist of 5-HT(1A) receptor, causes malformations of the CNS in ascidian embryos.
abstract: Serotonin (5-HT) is a neurotransmitter which is supposed to play a key role during development. In the last few years 5-HT receptors have been cloned in many animal species, and there is evidence that different 5-HT receptors are also present in ascidians. Ascidians and vertebrates are both members of the phylum Chordata and both have a dorsal tubular central nervous system. Embryos of the ascidian Phallusia mammillata have been treated with WAY-100635, a potent and selective 5-HT(1A) receptor antagonist. The larvae developed from treated embryos showed a dramatic reduction of their anterior sensory vesicles and the pigment of two sensory organs, the ocellus and the otolith. Immunofluorescence experiments with an anti beta-tubulin monoclonal antibody specific for the neural system showed that the anterior neural system of treated animals was radically altered by the action of the drug in a dose-dependent way. These results suggest that 5-HT plays a role in the development of the neural system in ascidians and its action is mediated by receptors similar to the members of the 5-HT(1A) receptor subtype of mammals.
authors.affiliation: Department of Biology, sez. Zoologia S.N. 7B, University of Milan, Via Celoria 26, 20133 Milan, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Pennati
authors.forename: Silvia
authors.initials: S
authors.lastname: Groppelli
authors.forename: Cristina
authors.initials: C
authors.lastname: Sotgia
authors.forename: Giuliana
authors.initials: G
authors.lastname: Zega
authors.forename: Mario
authors.initials: M
authors.lastname: Pestarino
authors.forename: Fiorenza
authors.initials: F
authors.lastname: De Bernardi
mesh_terms: D000818:Animals; D002490:Central Nervous System / Q000002:abnormalities / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004625:Embryo, Nonmammalian / Q000187:drug effects; D005455:Fluorescent Antibody Technique; D007814:Larva; D009475:Neurons, Afferent / Q000187:drug effects / Q000473:pathology; D010879:Piperazines / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology*; D012679:Sense Organs / Q000002:abnormalities / Q000187:drug effects / Q000473:pathology; D058829:Serotonin 5-HT1 Receptor Antagonists; D012702:Serotonin Antagonists / Q000494:pharmacology*; D014404:Tubulin / Q000276:immunology; D014561:Urochordata / Q000187:drug effects* / Q000196:embryology* / Q000254:growth & development
chemical_list: D010879:Piperazines; D011725:Pyridines; D058829:Serotonin 5-HT1 Receptor Antagonists; D012702:Serotonin Antagonists; D014404:Tubulin; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide