Role of NO generation in beta-adrenoceptor-mediated stimulation of rabbit airway ciliary motility.
To determine possible contribution of nitric oxide (NO) to the stimulatory action of beta-adrenoceptor agonist on ciliary motility, we measured ciliary beat frequency (CBF) of rabbit cultured tracheal epithelial cells by photoelectric method and NO release by specific amperometric sensors for this molecule in vitro. Salbutamol increased CBF, an effect that was potentiated by superoxide dismutase. Pretreatment of cells with NG-nitro-L-arginine methyl ester (L-NAME) attenuated the salbutamol-induced increase in CBF, causing a rightward displacement of the concentration-response curve by 2-2.5 log units, whereas NG-nitro-D-arginine methyl ester had no effect. The inhibitory effect of L-NAME was reversed by L-arginine but not by D-arginine. Immersion of the NO-selective electrode in the medium containing epithelial cells detected baseline current of 4.6-14.5 pA, which was abolished by L-NAME. Salbutamol dose-dependently increased the concentration of NO in the medium, the maximal increase being 56.2 +/- 5.3 nM (mean +/- SE; P < 0.001). These results suggest that NO is spontaneously released by airway epithelium and that the enhanced release of this molecule may play a role in the beta-adrenoceptor-mediated stimulation of ciliary motility.
Tamaoki
J
J
First Department of Medicine, Tokyo Women's Medical College, Japan.
Chiyotani
A
A
Kondo
M
M
Konno
K
K
D000420:Albuterol / Q000494:pharmacology*; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D002478:Cells, Cultured; D002923:Cilia / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D007700:Kinetics; D009068:Movement / Q000187:drug effects; D009092:Mucous Membrane / Q000187:drug effects / Q000502:physiology; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000502:physiology*; D010396:Penicillamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D011817:Rabbits; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000502:physiology*; D026423:S-Nitroso-N-Acetylpenicillamine; D013482:Superoxide Dismutase / Q000494:pharmacology; D013997:Time Factors; D014132:Trachea / Q000502:physiology*
D011943:Receptors, Adrenergic, beta; D009569:Nitric Oxide; D026423:S-Nitroso-N-Acetylpenicillamine; D001120:Arginine; D011433:Propranolol; D013482:Superoxide Dismutase; D010396:Penicillamine; D000420:Albuterol; D019331:NG-Nitroarginine Methyl Ester