Inhibition of cerebrospinal fluid formation by omeprazole.
Omeprazole, a specific inhibitor of H(+)-K(+)-activated ATPase, gave a dose-dependent inhibition of CSF production as determined by cerebroventriculocisternal perfusions in the rabbit. The reduction was 35% when the perfusate concentration of omeprazole was 10(-6) M and 25% after an intravenous dose of 0.2 mg/kg of omeprazole, respectively. A similarly substituted benzimidazol (H178/42) without H(+)-K(+)-ATPase-inhibiting properties did not affect CSF production at a perfusate concentration of 10(-5) M. Omeprazole in a concentration of 2 x 10(-4) M and more caused a significant but variable reduction in total and Na(+)-K(+)-ATPase activity in choroid plexus homogenates. However, in concentrations of 2 x 10(-5) M and less, no effect on total or Na(+)-K(+)-ATPase activity was obtained. Nor did omeprazole (2 x 10(-4) M) influence HCO3-ATPase. Choline uptake in isolated choroid plexus was significantly reduced by 86% in the presence of acid-pretreated omeprazole 2 x 10(-3) M, but was not affected by 2 x 10(-5) M omeprazole (intact or acid-pretreated). Thus, the mechanism for the marked inhibitory influence of omeprazole on CSF production is not yet evident. In doses causing even a 50% reduction of CSF production, no side effects were observed in contrast to Na(+)-K(+)-ATPase inhibitors such as ouabain.
Lindvall-Axelsson
M
M
Department of Medical Cell Research, University of Lund, Sweden.
Nilsson
C
C
Owman
C
C
Winbladh
B
B
D000251:Adenosine Triphosphatases / Q000378:metabolism; D000818:Animals; D002555:Cerebrospinal Fluid / Q000187:drug effects / Q000502:physiology*; D002794:Choline / Q000493:pharmacokinetics; D002831:Choroid Plexus / Q000378:metabolism*; D005260:Female; D017506:H(+)-K(+)-Exchanging ATPase; D008297:Male; D009853:Omeprazole / Q000494:pharmacology*; D010042:Ouabain / Q000494:pharmacology; D011817:Rabbits
D010042:Ouabain; D000251:Adenosine Triphosphatases; D017506:H(+)-K(+)-Exchanging ATPase; D009853:Omeprazole; D002794:Choline