title: Naftidrofuryl exerts antiserotonergic but no endothelin-receptor blocking effects in AS4.1 cells, juxtaglomerular cells and isolated perfused rat kidneys.
abstract: Naftidrofuryl, a 5-hydroxytryptamine 2 (5-HT 2 ) serotonergic receptor antagonist with vasodilator effects, has successfully been used for intermittent claudication, some forms of dementia, and glaucoma. Recently, an additional mode of action of naftidrofuryl (i.e., mixed endothelin receptor antagonism) has been suggested. However, in the current study naftidrofuryl was unable to block endothelin-3-induced free intracellular calcium increases, in contrast to a mixed endothelin receptor antagonist, bosentan. The inhibition of forskolin-induced renin secretion by endothelin-3 in primary cultures of mouse juxtaglomerular cells and by endothelin-1 in the isolated perfused rat kidney could not be blocked by naftidrofuryl. Naftidrofuryl was unable to block marked endothelin-1-induced renal vasoconstriction in isolated perfused rat kidney. In contrast, naftidrofuryl markedly attenuated serotonin-induced renal vasoconstriction and nearly completely blocked serotonin's renin inhibitory properties in isolated perfused rat kidney. The present results suggest that naftidrofuryl is a potent antagonist of serotonin's renal effects, but has no endothelin receptor-blocking properties.
authors.affiliation: Department of Medicine II, University of Regensburg, Regensburg, Germany.
authors.forename: Dierk
authors.initials: D
authors.lastname: Endemann
authors.forename: Frank
authors.initials: F
authors.lastname: Schweda
authors.forename: Mike
authors.initials: M
authors.lastname: Stubanus
authors.forename: Karl-Peter
authors.initials: KP
authors.lastname: Ittner
authors.forename: Michael
authors.initials: M
authors.lastname: Fischereder
authors.forename: Martin C
authors.initials: MC
authors.lastname: Kammerl
authors.forename: Bernhard K
authors.initials: BK
authors.lastname: Krämer
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D019332:Endothelin-1 / Q000378:metabolism; D019334:Endothelin-3 / Q000378:metabolism / Q000494:pharmacology; D007668:Kidney / Q000098:blood supply / Q000378:metabolism*; D007678:Kidney Glomerulus / Q000166:cytology / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009257:Nafronyl / Q000494:pharmacology*; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley; D017466:Receptors, Endothelin / Q000187:drug effects* / Q000378:metabolism; D012079:Renal Circulation / Q000187:drug effects; D012083:Renin / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism; D012702:Serotonin Antagonists / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects
chemical_list: D019332:Endothelin-1; D019334:Endothelin-3; D017466:Receptors, Endothelin; D012702:Serotonin Antagonists; D012701:Serotonin; D009257:Nafronyl; D012083:Renin; D002118:Calcium