Inhibition of skeletal muscle sarcoplasmic reticulum Ca2+-ATPase by nitric oxide.
The effects of nitric oxide on the activities of thapsigargin-sensitive sarcoplasmic reticulum Ca2+-ATPase (SERCA) and Ca2+ uptake by sarcoplasmic reticulum (SR) membranes prepared from white skeletal muscle of rabbit femoral muscle were studied. Pretreatment of the SR preparations with nitric oxide at concentrations of up to 250 microM for 1 min decreased the SERCA activity concentration dependently, and also decreased their Ca2+ uptake. Both these effects of nitric oxide were reversible. Inhibitors of guanylyl cyclase and protein kinase G (PKG) had no significant effect on the nitric oxide-induced inhibitions of SERCA and Ca2+ uptake. Moreover, dithiothreitol did not reverse the inhibitory effects of nitric oxide on SERCA and Ca2+ uptake. These findings suggest that nitric oxide inhibits SERCA, mainly SERCA 1, of rabbit femoral skeletal muscle by an action independent of the cyclic GMP-PKG system or oxidation of thiols, and probably by a direct action on SERCA protein.
Ishii
T
T
Department of Molecular Physiology and Biochemistry, Research Institute for Advanced Science and Technology, Osaka Prefecture University, Sakai, Japan.
Sunami
O
O
Saitoh
N
N
Nishio
H
H
Takeuchi
T
T
Hata
F
F
D000634:Aminoquinolines / Q000494:pharmacology; D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002120:Calcium Channel Agonists / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000494:pharmacology; D017869:Cyclic GMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D004229:Dithiothreitol / Q000494:pharmacology; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors / Q000502:physiology; D006493:Heparin / Q000494:pharmacology; D015544:Inositol 1,4,5-Trisphosphate / Q000494:pharmacology; D009569:Nitric Oxide / Q000494:pharmacology*; D010042:Ouabain / Q000494:pharmacology; D011817:Rabbits; D012433:Ryanodine / Q000494:pharmacology; D012519:Sarcoplasmic Reticulum / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D019284:Thapsigargin / Q000494:pharmacology; D013873:Thionucleotides / Q000494:pharmacology
D000634:Aminoquinolines; D002120:Calcium Channel Agonists; D002121:Calcium Channel Blockers; D013873:Thionucleotides; D012433:Ryanodine; C098740:8-bromo-beta-phenyl-1,N(2)-ethenoguanosine 3',5'-cyclic monophosphorothioate; D009569:Nitric Oxide; D002110:Caffeine; D010042:Ouabain; D019284:Thapsigargin; D015544:Inositol 1,4,5-Trisphosphate; D006493:Heparin; C041715:6-anilino-5,8-quinolinedione; D017869:Cyclic GMP-Dependent Protein Kinases; D006162:Guanylate Cyclase; D000252:Calcium-Transporting ATPases; D000254:Sodium-Potassium-Exchanging ATPase; D006152:Cyclic GMP; D002118:Calcium; D004229:Dithiothreitol