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Gallbladder Na+/H+ exchange activity is up-regulated prior to cholesterol crystal formation.

Publication ,  Journal Article
Narins, SC; Ramakrishnan, R; Park, EH; Smith, PR; Meyers, WC; Abedin, MZ
Published in: Eur J Clin Invest
August 2005

BACKGROUND: Gallbladder Na+ and H2O absorption are increased prior to gallstone formation and may promote cholesterol nucleation. Na+/H+ exchange (NHE) isoforms NHE2 and NHE3 are involved in gallbladder Na+ transport in prairie dogs. We examined whether increased gallbladder Na+ absorption observed during early gallstone formation is the result of NHE up-regulation. MATERIALS AND METHODS: Native gallbladder and primary cultures of gallbladder epithelial cells (GBECs) harvested from prairie dogs fed nonlithogenic (CON) or 1.2% cholesterol diet for varying lengths of time to induce cholesterol-saturated bile (PreCRYS), cholesterol crystals (CRYS), or gallstones (GS) were used. NHE activity was assessed by measuring dimethylamiloride-inhibitable 22Na+ uptake under H+ gradient in primary GBECs. HOE-694 was used to determine NHE2 and NHE3 contributions. NHE protein and mRNA expression were examined by Western and Northern blots, respectively. RESULTS: Gallbladder total NHE activity was 25.1 +/- 1.3 nmol mg protein(-1) min(-1) in the control and increased during gallstone formation peaking at the PreCRYS stage (98.4 +/- 3.9 nmol mg protein(-1) min(-1)). There was a shift in NHE activity from NHE2 to NHE3 as the animals progressed from no stones through the PreCRYS and CRYS stages to gallstones. The increase in NHE activity was partly caused by an increased Vmax without any change in K(Na)m. Both NHE2 and NHE3 protein increased moderately during the PreCRYS stage without increases in mRNA expression. CONCLUSIONS: Increased gallbladder Na+ absorption observed prior to crystal formation is in part caused by an increase NHE activity which is not fully accounted for by an increase in NHE proteins and mRNA levels but may be explained by enhanced localization in the membranes and/or altered regulation of NHE.

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Published In

Eur J Clin Invest

DOI

ISSN

0014-2972

Publication Date

August 2005

Volume

35

Issue

8

Start / End Page

514 / 522

Location

England

Related Subject Headings

  • Up-Regulation
  • Sodium-Hydrogen Exchangers
  • Sodium
  • RNA, Messenger
  • Protein Isoforms
  • Phospholipids
  • Male
  • General Clinical Medicine
  • Gallbladder
  • Epithelial Cells
 

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Narins, S. C., Ramakrishnan, R., Park, E. H., Smith, P. R., Meyers, W. C., & Abedin, M. Z. (2005). Gallbladder Na+/H+ exchange activity is up-regulated prior to cholesterol crystal formation. Eur J Clin Invest, 35(8), 514–522. https://doi.org/10.1111/j.1365-2362.2005.01520.x
Narins, S. C., R. Ramakrishnan, E. H. Park, P. R. Smith, W. C. Meyers, and M. Z. Abedin. “Gallbladder Na+/H+ exchange activity is up-regulated prior to cholesterol crystal formation.Eur J Clin Invest 35, no. 8 (August 2005): 514–22. https://doi.org/10.1111/j.1365-2362.2005.01520.x.
Narins SC, Ramakrishnan R, Park EH, Smith PR, Meyers WC, Abedin MZ. Gallbladder Na+/H+ exchange activity is up-regulated prior to cholesterol crystal formation. Eur J Clin Invest. 2005 Aug;35(8):514–22.
Narins, S. C., et al. “Gallbladder Na+/H+ exchange activity is up-regulated prior to cholesterol crystal formation.Eur J Clin Invest, vol. 35, no. 8, Aug. 2005, pp. 514–22. Pubmed, doi:10.1111/j.1365-2362.2005.01520.x.
Narins SC, Ramakrishnan R, Park EH, Smith PR, Meyers WC, Abedin MZ. Gallbladder Na+/H+ exchange activity is up-regulated prior to cholesterol crystal formation. Eur J Clin Invest. 2005 Aug;35(8):514–522.
Journal cover image

Published In

Eur J Clin Invest

DOI

ISSN

0014-2972

Publication Date

August 2005

Volume

35

Issue

8

Start / End Page

514 / 522

Location

England

Related Subject Headings

  • Up-Regulation
  • Sodium-Hydrogen Exchangers
  • Sodium
  • RNA, Messenger
  • Protein Isoforms
  • Phospholipids
  • Male
  • General Clinical Medicine
  • Gallbladder
  • Epithelial Cells