title: Furosemide-induced airway relaxation in guinea pigs: relation to Na-K-2Cl cotransporter function.
abstract: This study tested the hypothesis that airway relaxation to furosemide is mediated via the Na-K-2Cl cotransporter. If this mechanism exists in airway smooth muscle like in vascular smooth muscle, changes in airway relaxation should be associated with changes in Na-K-2Cl cotransporter function, and both should be substrate dependent. Tracheal rings from newborn guinea pigs were bathed in standard (STD) or varying low Cl- concentration ([Cl-]) N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid (HEPES). Isometric relaxation to 300 microM furosemide or 10(-8) to 10(-5) M salbutamol was measured. Airway segments were incubated with rubidium-86 (86Rb) in STD or varying low [Cl-] HEPES, with and without 300 microM furosemide or 25 microM salbutamol. Furosemide was unable to reduce 86Rb uptake at 10 mM [Cl-], although relaxation was still observed in 10 mM [Cl-]. Salbutamol did not affect 86Rb uptake. This study demonstrated that there is a furosemide-sensitive Na-K-2Cl cotransporter in newborn guinea pig trachea. However, the effect of furosemide on cotransporter function did not always directly correspond to differences in relaxation, suggesting that the Na-K-2Cl cotransporter may play a major, but not exclusive, role in furosemide-induced airway relaxation.
authors.affiliation: Department of Clinical Investigation, Tripler Army Medical Center, Honolulu, Hawaii 96859, USA.
authors.forename: S L
authors.initials: SL
authors.lastname: Lavallee
authors.forename: L M
authors.initials: LM
authors.lastname: Iwamoto
authors.forename: J R
authors.initials: JR
authors.lastname: Claybaugh
authors.forename: M V
authors.initials: MV
authors.lastname: Dressel
authors.forename: A K
authors.initials: AK
authors.lastname: Sato
authors.forename: K T
authors.initials: KT
authors.lastname: Nakamura
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001692:Biological Transport; D002034:Bumetanide / Q000494:pharmacology; D002352:Carrier Proteins / Q000187:drug effects / Q000378:metabolism*; D002712:Chlorides / Q000494:pharmacology; D004848:Epithelium / Q000502:physiology; D005665:Furosemide / Q000494:pharmacology*; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007537:Isometric Contraction; D007700:Kinetics; D009126:Muscle Relaxation / Q000187:drug effects* / Q000502:physiology; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology*; D012413:Rubidium / Q000493:pharmacokinetics; D028021:Sodium-Potassium-Chloride Symporters; D014132:Trachea / Q000187:drug effects / Q000502:physiology*
chemical_list: D002352:Carrier Proteins; D002712:Chlorides; D028021:Sodium-Potassium-Chloride Symporters; D002034:Bumetanide; D005665:Furosemide; D012413:Rubidium