Unknown

Dataset Information

0

Capsazepine, a synthetic vanilloid that converts the Na,K-ATPase to Na-ATPase.


ABSTRACT: Capsazepine (CPZ), a synthetic capsaicin analogue, inhibits ATP hydrolysis by Na,K-ATPase in the presence but not in the absence of K(+). Studies with purified membranes revealed that CPZ reduced Na(+)-dependent phosphorylation by interference with Na(+) binding from the intracellular side of the membrane. Kinetic analyses showed that CPZ stabilized an enzyme species that constitutively occluded K(+). Low-affinity ATP interaction with the enzyme was strongly reduced after CPZ treatment; in contrast, indirectly measured interaction with ADP was much increased, which suggests that composite regulatory communication with nucleotides takes place during turnover. Studies with lipid vesicles revealed that CPZ reduced ATP-dependent digitoxigenin-sensitive (22)Na(+) influx into K(+)-loaded vesicles only at saturating ATP concentrations. The drug apparently abolishes the regulatory effect of ATP on the pump. Drawing on previous homology modeling studies of Na,K-ATPase to atomic models of sarcoplasmic reticulum Ca-ATPase and on kinetic data, we propose that CPZ uncouples an Na(+) cycle from an Na(+)/K(+) cycle in the pump. The Na(+) cycle possibly involves transport through the recently characterized Na(+)-specific site. A shift to such an uncoupled mode is believed to produce pumps mediating uncoupled Na(+) efflux by modifying the transport stoichiometry of single pump units.

SUBMITTER: Mahmmoud YA 

PROVIDER: S-EPMC2234217 | biostudies-literature | 2008 Feb

REPOSITORIES: biostudies-literature

altmetric image

Publications

Capsazepine, a synthetic vanilloid that converts the Na,K-ATPase to Na-ATPase.

Mahmmoud Yasser A YA  

Proceedings of the National Academy of Sciences of the United States of America 20080129 5


Capsazepine (CPZ), a synthetic capsaicin analogue, inhibits ATP hydrolysis by Na,K-ATPase in the presence but not in the absence of K(+). Studies with purified membranes revealed that CPZ reduced Na(+)-dependent phosphorylation by interference with Na(+) binding from the intracellular side of the membrane. Kinetic analyses showed that CPZ stabilized an enzyme species that constitutively occluded K(+). Low-affinity ATP interaction with the enzyme was strongly reduced after CPZ treatment; in contr  ...[more]

Similar Datasets

| S-EPMC5240710 | biostudies-literature
| S-EPMC4016139 | biostudies-literature
2004-11-19 | GSE1134 | GEO
| S-EPMC8637647 | biostudies-literature
| S-EPMC11360054 | biostudies-literature
| S-EPMC1304497 | biostudies-literature
| S-EPMC2396460 | biostudies-literature
| S-EPMC3882478 | biostudies-literature
| S-EPMC4601662 | biostudies-literature
2023-10-05 | GSE242525 | GEO