Mechanism of bradykinin-induced cyclic GMP accumulation in bovine tracheal smooth muscle.
Bradykinin (10(-8) - 10(-5) M) caused a concentration-dependent increase in cyclic GMP (cGMP) production in bovine tracheal smooth muscle in the absence of epithelium. The effect was calcium-dependent and was inhibited by pyrogallol (10 microM) and methylene blue (10 microM). The inhibition of pyrogallol was reversed by superoxide dismutase (100 U/ml). Nitric oxide (NO) synthase inhibitors, NG-methyl-L-arginine (10-100 microM) and NG-nitro-L-arginine (10-100 microM) reduced cGMP accumulation induced by bradykinin in a concentration-dependent fashion, and the inhibition was reversed by L-arginine. Immunohistochemistry with a specific antibody against neuronal NO synthase from rat cerebellum showed positive staining localized in some nerve fibers. Bradykinin-induced cGMP accumulation appears to be related to the release of NO, part of which is probably synthesized in nonadrenergic noncholinergic nerve in bovine trachea.
Sheng
H
H
Signal Transduction Group, Abbott Laboratories, Abbott Park, Illinois 60064, USA.
Ishii
K
K
Förstermann
U
U
Murad
F
F
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001920:Bradykinin / Q000494:pharmacology*; D002118:Calcium / Q000494:pharmacology / Q000502:physiology; D002417:Cattle; D006152:Cyclic GMP / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D008751:Methylene Blue / Q000494:pharmacology; D009130:Muscle, Smooth / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D019335:Nitroarginine; D011748:Pyrogallol / Q000494:pharmacology; D013482:Superoxide Dismutase / Q000494:pharmacology; D014132:Trachea / Q000378:metabolism*; D019323:omega-N-Methylarginine
D004791:Enzyme Inhibitors; D011748:Pyrogallol; D019335:Nitroarginine; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase; D013482:Superoxide Dismutase; D006152:Cyclic GMP; D001920:Bradykinin; D002118:Calcium; D008751:Methylene Blue