cGMP modulation of Ca21 sensitivity in airway smooth muscle

Jones, Keith A., Gilbert Y. Wong, Christopher J. Jankowski, Masaki Akao, and David O. Warner. cGMP modulation of Ca21 sensitivity in airway smooth muscle. Am. J. Physiol. 276 (Lung Cell. Mol. Physiol. 20): L35–L40, 1999.—A b-escin-permeabilized canine tracheal smooth muscle preparation was used to test the hypothesis that cGMP decreases Ca21 sensitivity in airway smooth muscle primarily by inhibiting the membrane receptor-coupled mechanisms that regulate Ca21 sensitivity and not by inhibiting Ca21/calmodulin activation of the contractile proteins. 8-Bromo-cGMP (100 μM) had no effect on the free Ca21 concentration-response curves generated in the absence of muscarinic receptor stimulation. In the presence of 100 μM ACh plus 10 μM GTP, 8-bromo-cGMP (100 μM) caused a rightward shift of the free Ca21 concentration-response curve, significantly increasing the EC50 for free Ca21 from 0.35 6 0.03 to 0.75 6 0.06 μM; this effect of 8-bromo-cGMP was concentration dependent from 1 to 100 μM. 8-Bromo-cGMP (100 μM) decreased the level of regulatory myosin light chain (rMLC) phosphorylation for a given cytosolic Ca21 concentration but had no effect on the amount of isometric force produced for a given level of rMLC phosphorylation. These findings suggest that cGMP decreases Ca21 sensitivity in canine tracheal smooth muscle primarily by inhibiting the membrane receptor-coupled mechanisms that modulate the relationship between cytosolic Ca21 concentration and rMLC phosphorylation.