title: Bradykinin regulation of airway submucosal gland secretion: role of bradykinin receptor subtype.
abstract: To clarify the role of bradykinin receptor subtypes, we examined the effect of bradykinin on feline tracheal and human airway submucosal gland secretion using an isolated gland preparation. Bradykinin induced a significant increase in [3H]glycoconjugate secretion in a dose-dependent manner from isolated glands, which was significantly inhibited by D-Arg-(Hyp3, Thi5,8, D-Phe7)-bradykinin (the B2-receptor antagonist), whereas Des-Arg9-(Leu8)-bradykinin (B1-receptor antagonist) or indomethacin did not significantly alter it. Nitric oxide synthase inhibitor (nitro-L-arginine methyl ester) caused a significant inhibition of bradykinin-induced glycoconjugate secretion, which was reversed by the addition of L-arginine. Bradykinin evoked bidirectional current responses, and an initial inward current (Cl- current) was followed by an outward current (K+ current) of the acinar cells in a whole cell configuration by patch-clamp technique. Bradykinin induced an immediate increase in intracellular calcium concentration ([Ca2+]i) of the acinar cells followed by a prolonged plateau, and Ca2+ removal resulted in an initial increase alone. [Ca2+]i rise was significantly inhibited by the B2-receptor antagonist, whereas the B1-receptor antagonist did not significantly alter it. These findings suggest that B2-receptor stimulation and the resultant [Ca2+]i rise induced both mucus glycoprotein and electrolyte secretions, involving NO formation in airway submucosal gland cells.
authors.affiliation: First Department of Internal Medicine, Tohoku University School of Medicine, Sendai, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Nagaki
authors.forename: S
authors.initials: S
authors.lastname: Shimura
authors.forename: T
authors.initials: T
authors.lastname: Irokawa
authors.forename: T
authors.initials: T
authors.lastname: Sasaki
authors.forename: T
authors.initials: T
authors.lastname: Oshiro
authors.forename: M
authors.initials: M
authors.lastname: Nara
authors.forename: Y
authors.initials: Y
authors.lastname: Kakuta
authors.forename: K
authors.initials: K
authors.lastname: Shirato
mesh_terms: D000818:Animals; D001920:Bradykinin / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D002415:Cats; D004553:Electric Conductivity; D006801:Humans; D066298:In Vitro Techniques; D007425:Intracellular Membranes / Q000378:metabolism; D009092:Mucous Membrane / Q000378:metabolism / Q000502:physiology; D009994:Osmolar Concentration; D018002:Receptors, Bradykinin / Q000502:physiology*; D014132:Trachea / Q000378:metabolism* / Q000502:physiology
chemical_list: D018002:Receptors, Bradykinin; D001920:Bradykinin; D002118:Calcium