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Actions of antisecretory agents on proton transport in hog gastric microsomes
Abstract:
The properties of K+-stimulated ATP hydrolysis (K+-ATPase) and vesicular accumulation of H+ (H+ accumulation) in hog gastric microsomes were investigated. The microsomes consisted of smooth surfaced vesicular particles, 70-300 nm in diameter. Both the activities of ATPase and the vesicular accumulation of H+ were stimulated by K+ in the presence of Mg2+, and enhanced by the K+-ionophore, valinomycin. However, there were differences in regulation of K+-ATPase and H+ accumulation by K+ ions, i.e. K+ at concentrations higher than 10 mM decreased K+-ATPase activity but further enhanced H+ transport. This observation suggests that the two reactions are partly independent. The H+ accumulation was inhibited by omeprazole, fenoctimine, spermine, and NaSCN, but not by cimetidine, prostaglandin E2, and atropine. The inhibitory effect of omeprazole on H+ accumulation paralleled the inhibition of K+-ATPase, while fenoctimine, spermine, and NaSCN suppressed H+ accumulation, without inhibiting K+-ATPase, under appropriate concentrations. In addition, the spontaneous diffusion of H+ across the microsomal membrane was markedly enhanced by fenoctimine, but not by the other agents used. These results indicate that omeprazole inhibits H+ accumulation by inhibiting K+-ATPase, fenoctimine suppresses H+ accumulation mainly by increasing the loss of accumulated H+ from the microsomal vesicles, spermine and NaSCN reduce H+ accumulation by inhibiting the transport of H+ into microsomal vesicles.
Insights
Hog gastric microsomes exhibit K+-stimulated ATP hydrolysis (K+-ATPase) and H+ accumulation. Different agents differentially regulate these processes, suggesting partial independence and distinct mechanisms of action.
Area of Science:
- Biochemistry
- Cell Biology
- Physiology
Background:
- Hog gastric microsomes contain K+-stimulated ATP hydrolysis (K+-ATPase) and vesicular H+ accumulation.
- These processes are crucial for gastric acid secretion.
Purpose of the Study:
- To investigate the properties of K+-ATPase and H+ accumulation in hog gastric microsomes.
- To elucidate the regulatory mechanisms and identify agents affecting these functions.
Main Methods:
- Isolation and characterization of hog gastric microsomes.
- Measurement of K+-ATPase activity and vesicular H+ accumulation.
- Assessment of the effects of various agents, including K+ ions, valinomycin, omeprazole, fenoctimine, spermine, and NaSCN.
Main Results:
- Both K+-ATPase and H+ accumulation were stimulated by K+ and valinomycin.
- Higher K+ concentrations differentially affected K+-ATPase and H+ transport, indicating partial independence.
- Omeprazole inhibited H+ accumulation by inhibiting K+-ATPase.
- Fenoctimine, spermine, and NaSCN inhibited H+ accumulation through distinct mechanisms, including increased H+ diffusion (fenoctimine) or transport inhibition (spermine, NaSCN).
Conclusions:
- K+-ATPase and H+ accumulation in gastric microsomes are partly independent processes.
- Omeprazole directly inhibits K+-ATPase, thereby reducing H+ accumulation.
- Fenoctimine, spermine, and NaSCN affect H+ accumulation via mechanisms separate from K+-ATPase inhibition, highlighting diverse regulatory pathways.