This application-proposes continuation of experiments designed understanding of the regulation and control of electrolyte transport large intestine. We plan to characterize the properities of Na-H exchange that is present in normal rats and identify the mechanism of electroneutral Cl absorption. We will also establish a basolateral membrane vesicle preparation to define the mechanism of sodium exit from the coloncyte. Primary emphasis is directed to defining the mechanism by which sodium and chloride absorption is enhanced by short chain fatty acids (SCFA) and by corticosteroids. The ability of the colon to increase fluid and electrolyte absorption can represent an important method to compensate for altered small intestinal function. These studies will establish the mechanism of SCFA absorb-tion and how SCFA stimulate active sodium and chloride absorption and test the hypothesis that SCFA are absorbed by non-ionic diffusion of the protonated form, followed by its disassociation and the coupling of NaH and Cl-SCFA exchanges. It is well established that corticosteroids stimulate active sodium and chloride transport but there is uncertainty whether the action of glucocorticoids manifest distinct (i.e. from aldosterone) receptor specific effects on ion transport. These studies will identify the ion transport changes that aldosterone induces in the apical membrane of the rat distal colony and will determine whether glucocorticoids produce receptor- specific changes in electrolyte transport (and whether electroneutral Na-Cl absorption is exclusively controlled by glucocorticoids. Since sodium depletion induces an increase in electroneutral sodium-chloride absorption (not electrogenic Na absorption, as found in ths distal colon), we plan to establish whether aldosterone (or glucocorticoids) enhance this electroneutral Na absorptive process. Further, we plan to establish the nature of Dl-dependent Na-H exchange in this segment. We also plan to obtain colonic mucosa from organ donors and prepare apical membrane vesicles in order to identify mechanism of Na uptake across the luminal membrane of human large intestine. In studies, we will determine ion transport by measuring both unidirectional --Na and fluxes across isolated intact mucosa from the rat distal (and proximal) colon under voltage clamp conditions and ion uptake by apical and basolateral membranes prepared from rat distal colon and human large intestine from organ donors.
| Vucic, Esad; Alfadda, Tariq; MacGregor, Gordon G et al. (2015) Kir1.1 (ROMK) and Kv7.1 (KCNQ1/KvLQT1) are essential for normal gastric acid secretion: importance of functional Kir1.1. Pflugers Arch 467:1457-1468 |
| Ghosh, Sikha; Choritz, Lars; Geibel, John et al. (2006) Somatostatin modulates PI3K-Akt, eNOS and NHE activity in the ciliary epithelium. Mol Cell Endocrinol 253:63-75 |
| Kirchhoff, Philipp; Dave, Mital H; Remy, Christine et al. (2006) An amino acid transporter involved in gastric acid secretion. Pflugers Arch 451:738-48 |
| Winter, Christian; Schulz, Nicole; Giebisch, Gerhard et al. (2004) Nongenomic stimulation of vacuolar H+-ATPases in intercalated renal tubule cells by aldosterone. Proc Natl Acad Sci U S A 101:2636-41 |
| Fidzinski, Pawel; Salvador-Silva, Mercedes; Choritz, Lars et al. (2004) Inhibition of NHE-1 Na+/H+ exchanger by natriuretic peptides in ocular nonpigmented ciliary epithelium. Am J Physiol Cell Physiol 287:C655-63 |
| Ikuma, Mutsuhiro; Geibel, John; Binder, Henry J et al. (2003) Characterization of Cl-HCO3 exchange in basolateral membrane of rat distal colon. Am J Physiol Cell Physiol 285:C912-21 |
| Stehberger, Paul A; Schulz, Nicole; Finberg, Karin E et al. (2003) Localization and regulation of the ATP6V0A4 (a4) vacuolar H+-ATPase subunit defective in an inherited form of distal renal tubular acidosis. J Am Soc Nephrol 14:3027-38 |
| Kirchhoff, Philipp; Wagner, Carsten A; Gaetzschmann, Florian et al. (2003) Demonstration of a functional apical sodium hydrogen exchanger in isolated rat gastric glands. Am J Physiol Gastrointest Liver Physiol 285:G1242-8 |
| Krishnan, Selvi; Rajendran, Vazhaikkurichi M; Binder, Henry J (2003) Apical NHE isoforms differentially regulate butyrate-stimulated Na absorption in rat distal colon. Am J Physiol Cell Physiol 285:C1246-54 |
| Sangan, Pitchai; Rajendran, Vazhaikkurichi M; Geibel, John P et al. (2002) Cloning and expression of a chloride-dependent Na+-H+ exchanger. J Biol Chem 277:9668-75 |
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