| Homing in on bile acid physiology Cell Metabolism, Volume 4, Issue 6, 1 December 2006, Pages 423-424 Sander M. Houten Summary Fibroblast growth factor 15 (Fgf15), a hormone made by the terminal ileum in response to bile acids, represses hepatic bile acid biosynthesis. demonstrate that Fgf15 is also required for gallbladder filling. Summary | Full Text | PDF (119 kb) |
| A Genomewide Search Finds Major Susceptibility Loci for Gallbladder Disease on Chromosome 1 in Mexican Americans The American Journal of Human Genetics, Volume 78, Issue 3, 1 March 2006, Pages 377-392 Sobha Puppala, Gerald D. Dodd, Sharon Fowler, Rector Arya, Jennifer Schneider, Vidya S. Farook, Richard Granato, Thomas D. Dyer, Laura Almasy, Christopher P. Jenkinson, Andrew K. Diehl, Michael P. Stern, John Blangero and Ravindranath Duggirala Abstract Gallbladder disease (GBD) is one of the major digestive diseases. Its risk factors include age, sex, obesity, type 2 diabetes, and metabolic syndrome (MS). The prevalence of GBD is high in minority populations, such as Native and Mexican Americans. Ethnic differences, familial aggregation of GBD, and the identification of susceptibility loci for gallstone disease by use of animal models suggest genetic influences on GBD. However, the major susceptibility loci for GBD in human populations have not been identified. Using ultrasound-based information on GBD occurrence and a 10-cM gene map, we performed multipoint variance-components analysis to localize susceptibility loci for GBD. Phenotypic and genotypic data from 715 individuals in 39 low-income Mexican American families participating in the San Antonio Family Diabetes/Gallbladder Study were used. Two GBD phenotypes were defined for the analyses: (1) clinical or symptomatic GBD, the cases of cholecystectomies due to stones confirmed by ultrasound, and (2) total GBD, the clinical GBD cases plus the stone carriers newly diagnosed by ultrasound. With use of the National Cholesterol Education Program/Adult Treatment Panel III criteria, five MS risk factors were defined: increased waist circumference, hypertriglyceredemia, low high-density lipoprotein cholesterol, hypertension, and high fasting glucose. The MS risk-factor score (range 0–5) for a given individual was used as a single, composite covariate in the genetic analyses. After accounting for the effects of age, sex, and MS risk-factor score, we found stronger linkage signals for the symptomatic GBD phenotype. The highest LOD scores (3.7 and 3.5) occurred on chromosome 1p between markers and (1p36.21) and near marker (1p34.3), respectively. Other genetic locations (chromosomes 2p, 3q, 4p, 8p, 9p, 10p, and 16q) across the genome exhibited some evidence of linkage (LOD ⩾1.2) to symptomatic GBD. Some of these chromosomal regions corresponded with the genetic locations of loci, which influence gallstone formation in mouse models. In conclusion, we found significant evidence of major genetic determinants of symptomatic GBD on chromosome 1p in Mexican Americans. Abstract | Full Text | PDF (430 kb) |
| Asymmetries in H/K-ATPase and Cell Membrane Potentials Comprise a Very Early Step in Left-Right Patterning Cell, Volume 111, Issue 1, 4 October 2002, Pages 77-89 Michael Levin, Thorleif Thorlin, Kenneth R. Robinson, Taisaku Nogi and Mark Mercola Summary A pharmacological screen identified the H and K ATPase transporter as obligatory for normal orientation of the left-right body axis in . Maternal H/K-ATPase mRNA is symmetrically expressed in the 1-cell embryo but becomes localized during the first two cell divisions, demonstrating that asymmetry is generated within two hours postfertilization. Although H/K-ATPase subunit mRNAs are symmetrically localized in chick embryos, an endogenous H/K-ATPase-dependent difference in membrane voltage potential exists between the left and right sides of the primitive streak. In both species, pharmacologic or genetic perturbation of endogenous H/K-ATPase randomized the sided pattern of asymmetrically expressed genes and induced organ heterotaxia. Thus, LR asymmetry determination depends on a very early differential ion flux created by H/K-ATPase activity. Summary | Full Text | PDF (1997 kb) |
Copyright © 1983 The Biophysical Society. All rights reserved.
Biophysical Journal, Volume 43, Issue 3, 269-278, 1 September 1983
doi:10.1016/S0006-3495(83)84350-1
Research Article
J.F. García-Díaz, W. Nagel and A. Essig
The epithelial and cellular effects of clamping the transepithelial potential (Vt, mucosa reference) have been investigated in the Necturus gallbladder. Following initial equilibration at short circuit, tissue conductance gt was 4.1 +/- 1.2 (SD) mS/cm2, the apical potential Va was -76 +/- 8 mV, and the apical fractional voltage on brief voltage perturbation (fa = delta Va/delta Vt, reflecting the ratio of apical membrane to transcellular resistance) was 0.72 +/- 0.11 (21 gallbladders, 34 impalements). On clamping Vt at positive values, Va depolarized and fa decreased; at the same time gt decreased. Clamping Vt at negative values produced converse effects. All of the above changes were related directly to the magnitude of the clamping potential Vt and were reversed on return to the short circuit state. Effects of Vt on fa are not due to changes in the extracellular pathway resistances (which, however, contribute to gt). Furthermore, the effects of Vt on fa were abolished by the mucosal application of TEA or Ba, or acidification of the mucosal solution. Thus, these experiments disclose the presence of a voltage-dependent apical K conductance that increases with apical membrane depolarization. The calculated dose-response curve of TEA inhibition of apical conductance and the values of the apparent dissociation constant were in good agreement with those found for K channels in excitable tissues. Mucosal application of the Ca ionophore A23187 shifted the voltage dependence curve of fa to more negative values of Va without altering its shape. The effect of A23187 suggests a possible role of intracellular Ca in the modulation of the apical K channels.