title: Peripheral 5-HT7 receptors as a new target for prevention of lung injury and mortality in septic rats.
abstract: Sepsis is a complex pathophysiological event involving metabolic acidosis, systemic inflammatory response syndrome, tissue damage and multiple organ dysfunction syndrome. Although many new mechanisms are being investigated to enlighten the pathophysiology of sepsis, there is no effective treatment protocol yet. Presence of 5-HT7 receptors in immune tissues prompted us to hypothesize that these receptors have roles in inflammation and sepsis. We investigated the effects of 5-HT7 receptor agonists and antagonists on serum cytokine levels, lung oxidative stress, lung histopathology, nuclear factor κB (NF-κB) positivity and lung 5-HT7 receptor density in cecal ligation and puncture (CLP) induced sepsis model of rats. Agonist administration to septic rats increased survival time; decreased serum cytokine response against CLP; decreased oxidative stress and increased antioxidant system in lungs; decreased the tissue NF-κB immunopositivity, which is high in septic rats; and decreased the sepsis-induced lung injury. In septic rats, as a result of high inflammatory response, 5-HT7 receptor expression in lungs increased significantly and agonist administration, which decreased inflammatory response and related mortality, decreased the 5-HT7 receptor expression. In conclusion, all these data suggest that stimulation of 5-HT7 receptors may be a new therapeutic target for prevention of impaired inflammatory response related lung injury and mortality.
authors.affiliation: Atatürk University, Faculty of Pharmacy, Department of Pharmacology, Erzurum, Turkey.
authors.forename: Elif
authors.initials: E
authors.lastname: Cadirci
authors.forename: Zekai
authors.initials: Z
authors.lastname: Halici
authors.forename: Yasin
authors.initials: Y
authors.lastname: Bayir
authors.forename: Abdulmecit
authors.initials: A
authors.lastname: Albayrak
authors.forename: Emre
authors.initials: E
authors.lastname: Karakus
authors.forename: Beyzagul
authors.initials: B
authors.lastname: Polat
authors.forename: Deniz
authors.initials: D
authors.lastname: Unal
authors.forename: Sabri S
authors.initials: SS
authors.lastname: Atamanalp
authors.forename: Selina
authors.initials: S
authors.lastname: Aksak
authors.forename: Cemal
authors.initials: C
authors.lastname: Gundogdu
mesh_terms: D000818:Animals; D002432:Cecum / Q000601:surgery; D016207:Cytokines / Q000097:blood; D008168:Lung / Q000378:metabolism* / Q000473:pathology; D008297:Male; D058990:Molecular Targeted Therapy; D018384:Oxidative Stress / Q000187:drug effects; D010636:Phenols / Q000008:administration & dosage; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000276:immunology / Q000378:metabolism*; D018805:Sepsis / Q000276:immunology* / Q000628:therapy; D012702:Serotonin Antagonists / Q000008:administration & dosage; D017366:Serotonin Receptor Agonists / Q000008:administration & dosage; D013449:Sulfonamides / Q000008:administration & dosage; D000097782:NF-kappaB-Inducing Kinase
chemical_list: D016207:Cytokines; D010636:Phenols; D017346:Protein Serine-Threonine Kinases; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D013449:Sulfonamides; D000097782:NF-kappaB-Inducing Kinase; C404922:SB 269970; C104425:serotonin 7 receptor
keywords: 5-HT7 receptor; CLP; NF-κB; Rat; Sepsis