Previous work has focused on the acid-base and hemodynamic determinants of reabsorption in the rat proximal convoluted tubule (PCT). Factors that specifically affect sodium bicarbonate transport (e.g., luminal and peritubular bicarbonate concentrations/pH and luminal flow rate) have been differentiated from those that primarily alter sodium chloride reabsorption (e.g., peritubular [protein]). The mechanisms of these transport regulatory effects (whether on the active or passive transport components) have also been elucidated. Recently, free-flow micropuncture studies suggested marked axial heterogeneity of both bicarbonate and chloride transport in the PCT. The early PCT had an increased anion transport capacity and appeared to be regulated differently, exhibiting less inhibition by alkalemia on bicarbonate reabsorption but more flow-dependence for chloride reabsorption, compared to the late PCT. The present proposal is designed to extend previous investigations by examining the luminal and peritubular determinants of active and passive components of proximal bicarbonate and chloride reabsorption as a function of tubule length. In vivo microperfusion and free-flow micropuncture will be used to pursue the following specific purposes: (1) To determine whether the axial heterogeneity of anion transport in the PCT is an intrinsic property of the individual nephron segments or is a function of the axial profile of other luminal determinants or factors. (2) To compare the kinetics of selected luminal determinants, such as anion concentration and flow rate, on the active and passive components of bicarbonate and chloride reabsorption in the early and late PCT. (3) To quantitate and define the mechanism of the individual peritubular determinants, including [HCO3 ion]/pH, [protein], nerve activity and angiotensin II, on anion transport as a function of PCT length. (4) To examine and confirm the integrated effects of these determinants on early and late proximal reabsorption when several luminal and peritubular determinants of anion transport are simultaneously altered.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK037423-03
Application #
3236316
Study Section
General Medicine B Study Section (GMB)
Project Start
1986-07-01
Project End
1990-06-30
Budget Start
1988-07-01
Budget End
1990-06-30
Support Year
3
Fiscal Year
1988
Total Cost
Indirect Cost
Name
University of California San Francisco
Department
Type
Schools of Medicine
DUNS #
073133571
City
San Francisco
State
CA
Country
United States
Zip Code
94143
Wong, K R; Berry, C A; Cogan, M G (1996) Alpha 1-adrenergic control of chloride transport in the rat S1 proximal tubule. Am J Physiol 270:F1049-56
Wong, K R; Berry, C A; Cogan, M G (1995) Chloride transport in the rat S1 proximal tubule. Am J Physiol 268:F723-9
Wong, K R; Berry, C A; Cogan, M G (1995) Flow dependence of chloride transport in rat S1 proximal tubules. Am J Physiol 269:F870-5
Pollock, A S; Santiesteban, H L (1995) Calbindin expression in renal tubular epithelial cells. Altered sodium phosphate co-transport in association with cytoskeletal rearrangement. J Biol Chem 270:16291-301
Cogan, M G; Liu, F Y; Wong, P C et al. (1991) Comparison of inhibitory potency by nonpeptide angiotensin II receptor antagonists PD123177 and DuP 753 on proximal nephron and renal transport. J Pharmacol Exp Ther 259:687-91
Cogan, M G (1990) Angiotensin II: a powerful controller of sodium transport in the early proximal tubule. Hypertension 15:451-8
Liu, F Y; Cogan, M G (1990) Role of protein kinase C in proximal bicarbonate absorption and angiotensin signaling. Am J Physiol 258:F927-33
Xie, M H; Liu, F Y; Wong, P C et al. (1990) Proximal nephron and renal effects of DuP 753, a nonpeptide angiotensin II receptor antagonist. Kidney Int 38:473-9
Cogan, M G (1990) Regulation and control of bicarbonate reabsorption in the proximal tubule. Semin Nephrol 10:115-21
Liu, F Y; Cogan, M G (1990) Role of angiotensin II in glomerulotubular balance. Am J Physiol 259:F72-9

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