Bradykinin regulation of airway submucosal gland secretion: role of bradykinin receptor subtype.
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.
Nagaki
M
M
First Department of Internal Medicine, Tohoku University School of Medicine, Sendai, Japan.
Shimura
S
S
Irokawa
T
T
Sasaki
T
T
Oshiro
T
T
Nara
M
M
Kakuta
Y
Y
Shirato
K
K
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
D018002:Receptors, Bradykinin; D001920:Bradykinin; D002118:Calcium