Inhibitory characteristics of lead chloride in sodium- and potassium- dependent adenosinetriphosphatase preparations derived from kidney, brain, and heart of several species.
Inhibition of adenosinetriphosphatase (ATPase) by lead chloride (PbCl2) was studied in microsomal fractions or tissue homogenates of kidney, brain, and heart of several species, including humans. The concentration of PbCl2 causing 50% inhibition (I50) of Na+ + K+ ATPase activity varied from 8 X 10(-6) to 8 X 10(-5) M, depending on the species and organ of origin of the enzyme. The enzyme preparations derived from various parts of the kidney showed no differential sensitivity to PbCl2. These differences in sensitivity to lead were not related to specific activity of the enzyme or to the protein content of the preparations studied. Mg2+ ATPase, which contaminated the enzyme preparations to a variable degree, was 10--100 times more resistant to PbCl2 than was Na+ + K+-activated ATPase. The following more detailed studies were performed on the dog brain and/or kidney enzyme. The inhibition of microsomal Na+ + K+ ATPase was characterized by reversible kinetics. The inhibitory effect was antagonized by Na+, increased by Mg2+, and not altered by K+. ATP alone, or together with Mg2+, antagonized the inhibition. Disodium edetate prevented or reversed the inhibition. These inhibitory characteristics suggest that Pb2+ inhibits Na+ + K+ ATPase at the Na+-dependent phosphorylation site, and that ATP chelates Pb2+ in competition with Mg2+. Combining Pb2+ with ATP may not only result in a reduction of ATPase activity but also cause a relative ATP deficiency if lead is present in sufficiently high concentration.
D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors*; D000818:Animals; D001921:Brain / Q000201:enzymology*; D002415:Cats; D006224:Cricetinae; D004285:Dogs; D004492:Edetic Acid / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D007668:Kidney / Q000201:enzymology*; D007700:Kinetics; D007854:Lead / Q000494:pharmacology*; D009206:Myocardium / Q000201:enzymology; D010042:Ouabain / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism; D011817:Rabbits; D051381:Rats; D012964:Sodium / Q000378:metabolism; D013045:Species Specificity
D007854:Lead; D010042:Ouabain; D004492:Edetic Acid; D012964:Sodium; D000251:Adenosine Triphosphatases; D011188:Potassium