title: Respiratory-burst stimulants desensitize beta-2 adrenoceptors on human polymorphonuclear leukocytes.
abstract: We investigated the effect of respiratory-burst stimulants on beta-2 adrenoceptors in human polymorphonuclear leukocytes (PMNL). Pre-incubation of PMNL with these substances did not affect the number or affinity of the receptors but desensitized them, as shown by the "right-shift" in (-)-isoproterenol competition isotherms. H-7, an established protein kinase C inhibitor, and nimesulide, a new putative inhibitor of this enzyme, blunted both superoxide anion production and beta-2 adrenoceptor desensitization. A positive correlation was found between superoxide anion generation and the "right-shift" in isoproterenol competition isotherm (r = 0.92; p less than 0.01). Desensitization of beta-2 adrenoceptors was not due to superoxide anions per se since incubation of PMNL with superoxide anion scavengers (superoxide dismutase and catalase) did not modify the results.
authors.affiliation: Servizio di Endocrinologia, Ospedale L. Sacco, Vialba, Milan, Italy.
authors.forename: T
authors.initials: T
authors.lastname: Vago
authors.forename: G
authors.initials: G
authors.lastname: Norbiato
authors.forename: G
authors.initials: G
authors.lastname: Baldi
authors.forename: E
authors.initials: E
authors.lastname: Chebat
authors.forename: P
authors.initials: P
authors.lastname: Bertora
authors.forename: M
authors.initials: M
authors.lastname: Bevilacqua
mesh_terms: D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000319:Adrenergic beta-Antagonists / Q000378:metabolism; D001667:Binding, Competitive; D006105:Granulomatous Disease, Chronic / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000378:metabolism; D007546:Isoquinolines / Q000494:pharmacology; D007700:Kinetics; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D010879:Piperazines / Q000494:pharmacology; D011412:Propanolamines / Q000378:metabolism; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000378:metabolism*; D013481:Superoxides / Q000378:metabolism*
chemical_list: D000319:Adrenergic beta-Antagonists; D007546:Isoquinolines; D010879:Piperazines; D011412:Propanolamines; D011943:Receptors, Adrenergic, beta; D013481:Superoxides; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D011493:Protein Kinase C; D007545:Isoproterenol; C033394:CGP 12177