AJP - Lung Cellular and Molecular Physiology, Vol 260, Issue 6 489-L493, Copyright © 1991 by American Physiological Society
Generation of an endothelium-derived relaxing factor-like substance in bovine tracheal smooth muscle
H. Sheng, K. Ishii and F. Murad
Pharmaceutical Discovery, Abbott Laboratories, Abbott Park, Chicago, Illinois 60064.
The mechanism of the accumulation of guanosine 3',5'-cyclic monophosphate
(cGMP) induced by carbachol was investigated in bovine tracheal smooth
muscle preparations. The effects of carbachol on cGMP were prevented with
methylene blue, hemoglobin, or atropine, indicating that the increase of
cGMP induced by carbachol is due to the activation of muscarinic
cholinergic receptors and is mediated by the stimulation of soluble
guanylyl cyclase. The elevation in cGMP induced by carbachol was also
inhibited by the superoxide anion-generating compound pyrogallol (100
microM). This inhibition was reversed by superoxide dismutase (100 U/ml).
Furthermore, NG-methyl-L-arginine (100 microM) and NG-nitro-L-arginine (3
microM) inhibited cGMP accumulation induced by carbachol, and this was
reversed by the addition of L-arginine (1 mM). These results suggest that
an endothelium-derived relaxing factor-like substance is generated in the
course of carbachol-induced cGMP accumulation in bovine tracheal smooth
muscle and that the precursor of this substance is L-arginine.
