Diamine oxidase is the amiloride-binding protein and is inhibited by amiloride analogues.
Diamine oxidase (histaminase), an enzyme that oxidatively deaminates putrescine and histamine, was purified from human placenta and from pig kidney. Both NH2-terminal sequences are highly homologous to the human kidney amiloride-binding protein, previously thought to be a component of the amiloride-sensitive Na+ channel. Monoclonal antibodies raised against the pig kidney amiloride-binding protein immunoprecipitate a polypeptide with the same M(r) (105,000) as that of pig kidney diamine oxidase. That polypeptide has both diamine oxidase activity and the capacity to bind [3H]phenamil, a tritiated amiloride derivative. Cells stably transfected with human kidney amiloride-binding protein cDNA express a high diamine oxidase activity. In transfected cells as well as with the purified enzyme, this activity was inhibited by amiloride and by some of its derivatives, such as phenamil and ethylpropylamiloride. Amiloride inhibition seems to be due to drug binding at the active site of the enzyme. These data indicate that human placental diamine oxidase is identical to the human kidney amiloride-binding protein and that amiloride analogues may have wider physiological effects besides those on epithelial ion transport.
Novotny
W F
WF
Department of Medicine, University of California, San Diego Medical Center 92103.
Chassande
O
O
Baker
M
M
Lazdunski
M
M
Barbry
P
P
D000584:Amiloride / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology*; D006631:Amine Oxidase (Copper-Containing) / Q000037:antagonists & inhibitors / Q000302:isolation & purification / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000302:isolation & purification / Q000378:metabolism*; D003106:Colon / Q000378:metabolism; D018076:DNA, Complementary / Q000378:metabolism; D005260:Female; D006801:Humans; D007668:Kidney / Q000201:enzymology*; D007700:Kinetics; D008969:Molecular Sequence Data; D008970:Molecular Weight; D010920:Placenta / Q000201:enzymology*; D011247:Pregnancy; D017386:Sequence Homology, Amino Acid; D013552:Swine; D014162:Transfection
D000911:Antibodies, Monoclonal; D002352:Carrier Proteins; D018076:DNA, Complementary; C047088:phenylamil; D000584:Amiloride; D006631:Amine Oxidase (Copper-Containing); C065976:AOC1 protein, human