Document Detail

The future of the pump.
MedLine Citation:
PMID:  17575526     Owner:  NLM     Status:  MEDLINE    
Since it was discovered 3 decades ago the H,K-ATPase has come to be recognized as the key both to the generation and pharmacologic suppression of gastric acid secretion. Although 30 years of concerted research has answered many questions, it is perhaps not surprising that these efforts have raised many new and crucial issues that await elucidation. These can be divided into 5 broad categories that relate to structure, mechanism, regulation, trafficking, and macromolecular interactions. It is probably safe to predict that the growing sophistication of x-ray crystallographic techniques will yield a picture of the pump's molecular structure in the near future. These insights will, in turn, illuminate the details of the process through which enzymatic hydrolysis is coupled to ion translocation with unprecedented clarity. The gastric parietal cell employs an extremely complicated system of receptors, kinases, and second messengers to maintain tight control over pump function. Upon activation, this cell also performs a massive and elegant membrane trafficking transformation that plays a critical role in the regulatory process. Finally, it is becoming clear that every ion transport protein is a component in a large macromolecular complex whose constituents help to determine all of the transport system's fundamental physiologic properties. These are the major topics that will drive H,K pump research in the future, and it is likely that their resolution will create the foundations for the next generation of therapies aimed at controlling gastric acid secretion and its clinical consequences.
Michael J Caplan
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Review    
Journal Detail:
Title:  Journal of clinical gastroenterology     Volume:  41 Suppl 2     ISSN:  0192-0790     ISO Abbreviation:  J. Clin. Gastroenterol.     Publication Date:  2007 Jul 
Date Detail:
Created Date:  2007-06-18     Completed Date:  2007-08-21     Revised Date:  2008-07-10    
Medline Journal Info:
Nlm Unique ID:  7910017     Medline TA:  J Clin Gastroenterol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  S217-22     Citation Subset:  IM    
Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, CT 06520-8026, USA.
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MeSH Terms
Ankyrins / metabolism
Enzyme Activation
Gastric Acid / secretion*
Gastric Mucosa / enzymology*
H(+)-K(+)-Exchanging ATPase / chemistry,  metabolism*
Multiprotein Complexes / metabolism
Parietal Cells, Gastric / enzymology
Protein Binding
Protein Conformation
Protein Transport
Sodium-Potassium-Exchanging ATPase / metabolism
Grant Support
Reg. No./Substance:
0/Ankyrins; 0/Multiprotein Complexes; EC ATPase; EC ATPase

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