Effect of methyl isocyanate on rabbit cardiac Na+, K(+)-ATPase.
The present study describes the effect of methyl isocyanate (MIC) on rabbit cardiac microsomal Na+, K(+)-ATPase. Addition of MIC in vitro resulted in dose-dependent inhibition of Na+, K(+)-ATPase, Mg(2+)-ATPase and K(+)-activated p-nitrophenyl phosphatase (K(+)-PNPPase). Activation of Na+, K(+)-ATPase by ATP in the presence of MIC showed a decrease in Vmax with no change in Km. Similarly, activation of K+ PNPPase by PNPP in the presence of MIC showed a decrease in Vmax with no change in Km. The circular dichroism spectral studies revealed that MIC interaction with Na+, K(+)-ATPase led to a conformation of the protein wherein the substrates Na+ and K+ were no longer able to bind at the Na(+)- and K(+)-activation sites. The data suggest that the inhibition of Na+, K(+)-ATPase was non-competitive and occurred by interference with the dephosphorylation of the enzyme-phosphoryl complex.
Jeevaratnam
K
K
Division of Pharmacology and Toxicology, Defense Research and Development Establishment, India.
D009597:4-Nitrophenylphosphatase / Q000037:antagonists & inhibitors; D000255:Adenosine Triphosphate / Q000378:metabolism; D000814:Aniline Compounds / Q000378:metabolism; D000818:Animals; D000986:Antisickling Agents / Q000633:toxicity*; D017301:Ca(2+) Mg(2+)-ATPase / Q000037:antagonists & inhibitors; D002942:Circular Dichroism; D005260:Female; D017953:Isocyanates / Q000633:toxicity*; D008861:Microsomes / Q000201:enzymology; D009206:Myocardium / Q000201:enzymology*; D009943:Organophosphorus Compounds / Q000378:metabolism; D011817:Rabbits; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism
D000814:Aniline Compounds; D000986:Antisickling Agents; D017953:Isocyanates; D009943:Organophosphorus Compounds; C068798:4-aminophenylphosphate; D000255:Adenosine Triphosphate; C008461:methyl isocyanate; D009597:4-Nitrophenylphosphatase; D017301:Ca(2+) Mg(2+)-ATPase; D000254:Sodium-Potassium-Exchanging ATPase