The objectives are to further define the factors involved in regulation of epithelial ion transport. Specifically, the site(s) and mechanisms by which putative endogenous regulators of intestinal ion transport alter absorption and secretion of electrolytes by the rabbit descending colon in vitro will be investigated. Measurements of transepithelial ion fluxes, intracellular potentials and ion activities will be conducted. These techniques are designed to further define: (1) the effects of putative endogenous mediators of intestinal ion transport on the transepithelial transport of Na, K and Cl in the colon; (2) the effects of these mediators on intracellular membrane potentials, membrane resistances and intracellular ion activites; (3) the site(s) of action of these mediators; and (4) the role of calmodulin and prostaglandins in stimulus-secretion coupling in the intestine. Results should provide information concerning the effects of endogenous regulators on intestinal ion transport and the sites and mechanisms by which absorptive and secretory stimuli act. Such information is essential to allow scientifically rational therapeutic approaches to the treatment of disorders of salt and water transport by the intestine. Furthermore, since the transport characteristics of a variety of absorptive and secretory epithelial are similar, studies of the absorptive and secretory mechanisms present in this epithelia may provide important information concerning the pathophysiology of intestinal transport processes in particular and the physiology of absorptive and secretory epithelia in general.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK038295-02
Application #
3237536
Study Section
General Medicine A Subcommittee 2 (GMA)
Project Start
1986-09-29
Project End
1989-08-31
Budget Start
1987-09-01
Budget End
1988-08-31
Support Year
2
Fiscal Year
1987
Total Cost
Indirect Cost
Name
Smithkline Beecham, Plc
Department
Type
DUNS #
City
Philadelphia
State
PA
Country
United States
Zip Code
19101
Smith, P L (1992) Effects of the neuroimmune mediators, peptidoleukotrienes, endothelin, and interleukin-1 on intestinal ion transport. Ann N Y Acad Sci 664:260-74
Jett, M F; Marshall, P; Fondacaro, J D et al. (1991) Action of peptidoleukotrienes on ion transport in rabbit distal colon in vitro. J Pharmacol Exp Ther 257:698-705
Wolfgang, G H; Gandolfi, A J; Nagle, R B et al. (1990) Assessment of S-(1,2-dichlorovinyl)-L-cysteine induced toxic events in rabbit renal cortical slices. Biochemical and histological evaluation of uptake, covalent binding, and toxicity. Chem Biol Interact 75:153-70
Chiossone, D C; Simon, P L; Smith, P L (1990) Interleukin-1: effects on rabbit ileal mucosal ion transport in vitro. Eur J Pharmacol 180:217-28
Smith, P L; Chiossone, D C; McCafferty, G P (1990) Characterization of LTC4 effects on rabbit ileal mucosa in vitro. Naunyn Schmiedebergs Arch Pharmacol 341:94-100
Elton, E; Chiossone, D C; McCafferty, G P et al. (1989) SK&F 104353: selective antagonism of peptidoleukotrine-induced changes in electrolyte transport by rat ileal mucosa in vitro. J Pharmacol Exp Ther 251:484-9
Finley, R B; Smith, P L (1989) Stimulation of chloride secretion by N-formyl-methionylleucylphenylalanine (FMLP) in rabbit ileal mucosa. J Physiol 417:403-19
Smith, P L; McCafferty, G P; Fondacaro, J D et al. (1988) Effects of putative thromboxane receptor agonists and antagonists on rat small intestinal ion transport. J Pharmacol Exp Ther 247:143-9
Smith, P L; Montzka, D P; McCafferty, G P et al. (1988) Effect of sulfidopeptide leukotrienes D4 and E4 on ileal ion transport in vitro in the rat and rabbit. Am J Physiol 255:G175-83