title: Differential regulation of oxidative stress and cytokine production by endothelin ETAand ETBreceptors in superoxide anion-induced inflammation and pain in mice.
abstract: The present study investigated whether endothelin-1 acts via ETAor ETBreceptors to mediate superoxide anion-induced pain and inflammation. Mice were treated with clazosentan (ETAreceptor antagonist) or BQ-788 (ETBreceptor antagonist) prior to stimulation with the superoxide anion donor, KO2. Intraplantar treatment with 30 nmol of clazosentan or BQ-788 reduced mechanical hyperalgesia (47% and 42%), thermal hyperalgesia (68% and 76%), oedema (50% and 30%); myeloperoxidase activity (64% and 32%), and overt-pain like behaviours, such as paw flinching (42% and 42%) and paw licking (38% and 62%), respectively. Similarly, intraperitoneal treatment with 30 nmol of clazosentan or BQ-788 reduced leukocyte recruitment to the peritoneal cavity (58% and 32%) and abdominal writhing (81% and 77%), respectively. Additionally, intraplantar treatment with clazosentan or BQ-788 decreased spinal (45% and 41%) and peripheral (47% and 47%) superoxide anion production as well as spinal (47% and 47%) and peripheral (33% and 54%) lipid peroxidation, respectively. Intraplantar treatment with clazosentan, but not BQ-788, reduced spinal (71%) and peripheral (51%) interleukin-1 beta as well as spinal (59%) and peripheral (50%) tumor necrosis factor-alpha production. Therefore, the present study unveils the differential mechanisms by which ET-1, acting on ETAor ETBreceptors, regulates superoxide anion-induced inflammation and pain.
authors.affiliation: a Departamento de Ciências Patológicas, Centro de Ciências Biológicas , Universidade Estadual de Londrina , Londrina , Brazil.
authors.forename: Victor
authors.initials: V
authors.lastname: Fattori
authors.affiliation: a Departamento de Ciências Patológicas, Centro de Ciências Biológicas , Universidade Estadual de Londrina , Londrina , Brazil.
authors.forename: Karla G G
authors.initials: KG
authors.lastname: Serafim
authors.affiliation: a Departamento de Ciências Patológicas, Centro de Ciências Biológicas , Universidade Estadual de Londrina , Londrina , Brazil.
authors.forename: Ana C
authors.initials: AC
authors.lastname: Zarpelon
authors.affiliation: a Departamento de Ciências Patológicas, Centro de Ciências Biológicas , Universidade Estadual de Londrina , Londrina , Brazil.
authors.forename: Sergio M
authors.initials: SM
authors.lastname: Borghi
authors.affiliation: a Departamento de Ciências Patológicas, Centro de Ciências Biológicas , Universidade Estadual de Londrina , Londrina , Brazil.
authors.forename: Felipe A
authors.initials: FA
authors.lastname: Pinho-Ribeiro
authors.affiliation: b Departamento de Farmacologia, Faculdade de Medicina de Ribeirão Preto , Universidade de São Paulo , Ribeirão Preto , Brazil.
authors.forename: José C
authors.initials: JC
authors.lastname: Alves-Filho
authors.affiliation: b Departamento de Farmacologia, Faculdade de Medicina de Ribeirão Preto , Universidade de São Paulo , Ribeirão Preto , Brazil.
authors.forename: Thiago M
authors.initials: TM
authors.lastname: Cunha
authors.affiliation: b Departamento de Farmacologia, Faculdade de Medicina de Ribeirão Preto , Universidade de São Paulo , Ribeirão Preto , Brazil.
authors.forename: Fernando Q
authors.initials: FQ
authors.lastname: Cunha
authors.affiliation: c Departamento de Ciências Farmacêuticas, Centro de Ciências da Saúde , Universidade Estadual de Londrina , Londrina , Brazil.
authors.forename: Rúbia
authors.initials: R
authors.lastname: Casagrande
authors.affiliation: a Departamento de Ciências Patológicas, Centro de Ciências Biológicas , Universidade Estadual de Londrina , Londrina , Brazil.
authors.forename: Waldiceu A
authors.initials: WA
authors.lastname: Verri
mesh_terms: D000818:Animals; D016207:Cytokines / Q000096:biosynthesis*; D065130:Endothelin A Receptor Antagonists / Q000494:pharmacology; D007249:Inflammation / Q000378:metabolism*; D008297:Male; D051379:Mice; D018384:Oxidative Stress; D010146:Pain / Q000378:metabolism*; D044022:Receptor, Endothelin A / Q000502:physiology*; D044023:Receptor, Endothelin B / Q000502:physiology*; D013481:Superoxides / Q000378:metabolism*
chemical_list: D016207:Cytokines; D065130:Endothelin A Receptor Antagonists; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D013481:Superoxides
keywords: BQ-788; clazosentan; hyperalgesia; interleukin-1β; leukocyte recruitment; lipid peroxidation; nitric oxide; nociception; oedema; tumor necrosis factor-α