S-nitrosoglutathione-induced decrease in calcium sensitivity of airway smooth muscle.
The purpose of this study was to examine whether the nitric oxide donor S-nitrosoglutathione (GSNO) relaxes canine tracheal smooth muscle (CTSM) strips by decreasing Ca(2+) sensitivity [i.e., the amount of force for a given intracellular Ca(2+) concentration ([Ca(2+)](i))]. We further investigated whether GSNO decreases Ca(2+) sensitivity by altering the relationship between regulatory myosin light chain (rMLC) phosphorylation and [Ca(2+)](i) and the relationship between force and rMLC phosphorylation. GSNO (100 microM) relaxed intact CTSM strips contracted with 45 mM KCl by decreasing Ca(2+) sensitivity in comparison to control strips without significantly decreasing [Ca(2+)](i). GSNO reduced the amount of rMLC phosphorylation for a given [Ca(2+)](i) but did not affect the relationship between isometric force and rMLC phosphorylation. These results show that in CTSM strips contracted with KCl, GSNO decreases Ca(2+) sensitivity by affecting the level of rMLC phosphorylation for a given [Ca(2+)](i), suggesting that myosin light chain kinase is inhibited or that smooth muscle protein phosphatases are activated by GSNO.
Pabelick
C M
CM
Department of Anesthesiology, Mayo Clinic and Foundation, Rochester, Minnesota 55905, USA.
Warner
D O
DO
Perkins
W J
WJ
Jones
K A
KA
D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology*; D004285:Dogs; D005260:Female; D005978:Glutathione / Q000031:analogs & derivatives* / Q000494:pharmacology; D066298:In Vitro Techniques; D007425:Intracellular Membranes / Q000378:metabolism; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D018994:Myosin Light Chains / Q000378:metabolism; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D009603:Nitroso Compounds / Q000494:pharmacology*; D009994:Osmolar Concentration; D010766:Phosphorylation / Q000187:drug effects; D026422:S-Nitrosoglutathione; D014132:Trachea / Q000187:drug effects* / Q000502:physiology
D018994:Myosin Light Chains; D020030:Nitric Oxide Donors; D009603:Nitroso Compounds; D026422:S-Nitrosoglutathione; D005978:Glutathione; D002118:Calcium