Competitive inhibition of mouse brain nitric oxide synthase by amiloride: a case for enzyme cross-inhibition.
Amiloride, a diuretic and antihypertensive drug, inhibits Na+ transporting systems, diamine oxidases and the human urinary plasminogen activator. Present results indicate that amiloride is a competitive inhibitor of mouse brain nitric oxide synthase (NOS; Ki = 4.5 x 10(-4) M, at pH 7.5 and 37.0 degrees C), but not a nitric oxide (NO) precursor, representing a case for enzyme cross-inhibition. The decreased levels of NO, as a consequence of NOS inhibition, might induce some clinically-adverse amiloride reactions, such as an unexpected reduced antihypertensive effect.
Ascenzi
P
P
Department of Biology, Third University of Rome, Italy. ascenzi@bio.uniroma3.it
Federico
R
R
Menegatti
E
E
Venturini
G
G
D000584:Amiloride / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001921:Brain / Q000201:enzymology*; D004232:Diuretics / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D008297:Male; D051379:Mice; D017942:Nitric Acid / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010960:Plasminogen Activators / Q000037:antagonists & inhibitors / Q000652:urine
D004232:Diuretics; D017942:Nitric Acid; D000584:Amiloride; D001120:Arginine; D019001:Nitric Oxide Synthase; D010960:Plasminogen Activators