cGMP modulation of Ca2+sensitivity in airway smooth muscle.

Academic Article

Abstract

  • A β-escin-permeabilized canine tracheal smooth muscle preparation was used to test the hypothesis that cGMP decreases Ca2+sensitivity in airway smooth muscle primarily by inhibiting the membrane receptor-coupled mechanisms that regulate Ca2+sensitivity and not by inhibiting Ca2+/calmodulin activation of the contractile proteins. 8-Bromo-cGMP (100 μM) had no effect on the free Ca2+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 Ca2+concentration-response curve, significantly increasing the EC50for free Ca2+from 0.35 ± 0.03 to 0.75 ± 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 Ca2+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 Ca2+sensitivity in canine tracheal smooth muscle primarily by inhibiting the membrane receptor-coupled mechanisms that modulate the relationship between cytosolic Ca2+concentration and rMLC phosphorylation.
  • Authors

    Keywords

  • acetylcholine, calcium sensitivity, fura 2, guanosine 3′,5′-cyclic monophosphate, guanosine 5′-O-(3-thiotriphosphate), myosin light chain phosphorylation, nitrovasodilators, trachea, β-escin
  • Digital Object Identifier (doi)

    Pubmed Id

  • 20827702
  • Author List

  • Jones KA; Wong GY; Jankowski CJ; Akao M; Warner DO
  • Start Page

  • L35
  • End Page

  • L40
  • Volume

  • 276
  • Issue

  • 1