title: Muscarinic receptors mediate the endocrine-disrupting effects of an organophosphorus insecticide in zebrafish.
abstract: The glucocorticoid cortisol, the end product of hypothalamus-pituitary-interrenal axis in zebrafish (Danio rerio), is synthesized via steroidogenesis and promotes important physiological regulations in response to a stressor. The failure of this axis leads to inability to cope with environmental challenges preventing adaptive processes in order to restore homeostasis. Pesticides and agrichemicals are widely used, and may constitute an important class of environmental pollutants when reach aquatic ecosystems and nontarget species. These chemical compounds may disrupt hypothalamus-pituitary-interrenal axis by altering synthesis, structure or function of its constituents. We present evidence that organophosphorus exposure disrupts stress response by altering the expression of key genes of the neural steroidogenesis, causing downregulation of star, hsp70, and pomc genes. This appears to be mediated via muscarinic receptors, since the muscarinic antagonist scopolamine blocked these effects.
authors.affiliation: Programa de Pós-graduação em Farmacologia, Universidade Federal de Santa Maria (UFSM), Av. Roraima, 1000, Cidade Universitária, Camobi, Santa Maria, RS, 97105-900, Brazil.
authors.forename: João Gabriel
authors.initials: JG
authors.lastname: Santos da Rosa
authors.affiliation: Programa de Pós-graduação em Farmacologia, Universidade Federal de Santa Maria (UFSM), Av. Roraima, 1000, Cidade Universitária, Camobi, Santa Maria, RS, 97105-900, Brazil.|Faculdade de Agronomia e Medicina Veterinária, Universidade de Passo Fundo (UPF), BR 285, São José, Passo Fundo, RS, 99052-900, Brazil.
authors.forename: Heloísa Helena de
authors.initials: HH
authors.lastname: Alcântara Barcellos
authors.affiliation: Faculdade de Agronomia e Medicina Veterinária, Universidade de Passo Fundo (UPF), BR 285, São José, Passo Fundo, RS, 99052-900, Brazil.
authors.forename: Michele
authors.initials: M
authors.lastname: Fagundes
authors.affiliation: Faculdade de Agronomia e Medicina Veterinária, Universidade de Passo Fundo (UPF), BR 285, São José, Passo Fundo, RS, 99052-900, Brazil.
authors.forename: Cristiane
authors.initials: C
authors.lastname: Variani
authors.affiliation: Faculdade de Agronomia e Medicina Veterinária, Universidade de Passo Fundo (UPF), BR 285, São José, Passo Fundo, RS, 99052-900, Brazil.
authors.forename: Mainara
authors.initials: M
authors.lastname: Rossini
authors.affiliation: Programa de Pós-graduação em Farmacologia, Universidade Federal de Santa Maria (UFSM), Av. Roraima, 1000, Cidade Universitária, Camobi, Santa Maria, RS, 97105-900, Brazil.
authors.forename: Fabiana
authors.initials: F
authors.lastname: Kalichak
authors.affiliation: Programa de Pós-graduação em Farmacologia, Universidade Federal de Santa Maria (UFSM), Av. Roraima, 1000, Cidade Universitária, Camobi, Santa Maria, RS, 97105-900, Brazil.
authors.forename: Gessi
authors.initials: G
authors.lastname: Koakoski
authors.affiliation: Programa de Pós-graduação em Farmacologia, Universidade Federal de Santa Maria (UFSM), Av. Roraima, 1000, Cidade Universitária, Camobi, Santa Maria, RS, 97105-900, Brazil.
authors.forename: Thiago
authors.initials: T
authors.lastname: Acosta Oliveira
authors.affiliation: Programa de Pós-graduação em Farmacologia, Universidade Federal de Santa Maria (UFSM), Av. Roraima, 1000, Cidade Universitária, Camobi, Santa Maria, RS, 97105-900, Brazil.|Faculdade de Agronomia e Medicina Veterinária, Universidade de Passo Fundo (UPF), BR 285, São José, Passo Fundo, RS, 99052-900, Brazil.
authors.forename: Renan
authors.initials: R
authors.lastname: Idalencio
authors.affiliation: Faculdade de Agronomia e Medicina Veterinária, Universidade de Passo Fundo (UPF), BR 285, São José, Passo Fundo, RS, 99052-900, Brazil.|Programa de Pós-graduação em Bioexperimentação, Universidade de Passo Fundo (UPF), BR 285, São José, Passo Fundo, RS, 99052-900, Brazil.
authors.forename: Rafael
authors.initials: R
authors.lastname: Frandoloso
authors.affiliation: Programa de Pós-Graduação em Farmacologia e Terapêutica, ICBS, Universidade Federal do Rio Grande do Sul (UFRGS), Rua Sarmento Leite 500, sala 305, Centro Histórico, Porto Alegre, RS, 90050-170, Brazil.
authors.forename: Angelo L
authors.initials: AL
authors.lastname: Piato
authors.affiliation: Programa de Pós-graduação em Farmacologia, Universidade Federal de Santa Maria (UFSM), Av. Roraima, 1000, Cidade Universitária, Camobi, Santa Maria, RS, 97105-900, Brazil.|Faculdade de Agronomia e Medicina Veterinária, Universidade de Passo Fundo (UPF), BR 285, São José, Passo Fundo, RS, 99052-900, Brazil.|Programa de Pós-graduação em Bioexperimentação, Universidade de Passo Fundo (UPF), BR 285, São José, Passo Fundo, RS, 99052-900, Brazil.
authors.forename: Leonardo
authors.initials: L
authors.lastname: José Gil Barcellos
mesh_terms: D000818:Animals; D052244:Endocrine Disruptors / Q000633:toxicity*; D050884:HSP72 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D006854:Hydrocortisone / Q000378:metabolism; D007306:Insecticides / Q000633:toxicity*; D008124:Locomotion / Q000187:drug effects; D008743:Methyl Parathion / Q000633:toxicity*; D018727:Muscarinic Antagonists / Q000494:pharmacology; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D011333:Pro-Opiomelanocortin / Q000235:genetics / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011976:Receptors, Muscarinic / Q000378:metabolism*; D012601:Scopolamine / Q000494:pharmacology; D014874:Water Pollutants, Chemical / Q000633:toxicity*; D015027:Zebrafish / Q000378:metabolism*; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism; D000098682:Steroidogenic Acute Regulatory Protein
chemical_list: D052244:Endocrine Disruptors; D050884:HSP72 Heat-Shock Proteins; D007306:Insecticides; D018727:Muscarinic Antagonists; D010750:Phosphoproteins; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D011976:Receptors, Muscarinic; D014874:Water Pollutants, Chemical; D029961:Zebrafish Proteins; C474117:pomca protein, zebrafish; D000098682:Steroidogenic Acute Regulatory Protein; D008743:Methyl Parathion; D011333:Pro-Opiomelanocortin; D012601:Scopolamine; D006854:Hydrocortisone
keywords: Danio rerio; acetylcholine receptors; methyl-parathion; scopolamine; steroidogenesis