Environmental differences of a pyridine derivative (AU-1421)-access sites between (H+,K+)-ATPase and (Na+,K+)-ATPase.
We investigated the environmental differences of a pyridine derivative-access sites between hog gastric (H+,K+)-ATPase and dog kidney (Na+,K+)-ATPase. The environmental differences are inferred from the marked contrasts in inhibition properties of (Z)-5-methyl-2-[2-(1-naphthyl)ethenyl]-4-piperidinopyridine hydrochloride (AU-1421) between the two adenosine triphosphatases (ATPases). AU-1421 is a hydrophobic pyridine derivative which inhibits (H+,K+)-ATPase and (Na+,K+)-ATPase competitively with respect to K+. AU-1421 inhibition of (Na+,K+)-ATPase activity is preincubation time-dependent, pH-independent (pH 6.4-8.4), and hardly reversible by dialysis. These features are opposite to those found with the gastric (H+,K+)-ATPase. Furthermore, in the presence of dilute sodium dodecyl sulfate (30-120 microM), the inhibitory potency of AU-1421 for (Na+,K+)-ATPase is increased, whereas the inhibitory potency for (H+,K+)-ATPase is decreased. These results favor proposals that protonated species of AU-1421 interact with its access-site of (H+,K+)-ATPase at the exterior surface of the enzyme molecule by ionic interaction, whereas AU-1421 interacts with its access-site of (NA+,K+)-ATPase at the interior domain of the enzyme molecule predominantly by hydrophobic interaction. The differences indicate the existence of a different feature of K(+)-access sites between the two ATPases.
Hioki
Y
Y
Central Research Laboratories, Banyu Pharmaceutical Co., Ltd., Tokyo, Japan.
Takada
J
J
Hidaka
Y
Y
Yano
M
M
D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors*; D000818:Animals; D004285:Dogs; D017506:H(+)-K(+)-Exchanging ATPase; D006863:Hydrogen-Ion Concentration; D009281:Naphthalenes / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology*; D012967:Sodium Dodecyl Sulfate / Q000494:pharmacology; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors*; D012995:Solubility; D013552:Swine
D009281:Naphthalenes; D011725:Pyridines; C063370:AU 1421; D012967:Sodium Dodecyl Sulfate; D000251:Adenosine Triphosphatases; D017506:H(+)-K(+)-Exchanging ATPase; D000254:Sodium-Potassium-Exchanging ATPase