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.
Signal Transduction Group, Abbott Laboratories, Abbott Park, Illinois 60064, USA.
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Sheng
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Ishii
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Förstermann
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Murad
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