The long-term aim of the proposed studies is to elucidate the mechanisms whereby the proximal tubule (PT) effects adaptations in its transport functions in response to a reduction in renal mass. The present studies will focus upon a single transport process, i.e. Na+-H+ antiport in the luminal membrane. The first group of studies will examine the effects of high luminal flow rates on fluid reabsorption and Na+-H+ antiport in the normal rabbit PT. The increased rate of fluid reabsorption induced by a high flow rate over a prolonged period persists when flow rate is reduced to normal values indicating that an intrinsic adaptation of cellular function has occurred. These studies will examine the possibility that distention of the tubule wall acts as a mechanical stimulus to prostaglandin production by the PT cell and that PGE2, alone or together with other prostaglandins, directly stimulates the activity of the Na+-H+ antiporter. These studies should explain how the proximal tubule adapts to long-term changes in filtration rate. The second group of studies will examine the response of the Na+-H+ antiporter in intact PT cells to hormones, including alpha and beta adrenergic agents, parathyroid hormone, angiotensin II, dopamine and insulin. The hormones which stimulate or inhibit this process will be identified and adaptations in the sensitivity and/or responsiveness of PT cells obtained from animals with reduced renal mass will be evaluated. If adaptations in the response of Na+-H+ antiport to specific hormones are found, a mediator-role for endogenous prostaglandins will again be sought, i.e. do endogenous prostaglandins act as the mediators of hormone action on the transport process and does inhibition of prostaglandin synthesis reverse the adaptation? Taken together, these studies should provide new insights into the mechanisms whereby adaptations of proximal tubular Na+-H+ exchange are mediated in response to a reduction in renal mass.
| Kurtz, I (1991) Role of ammonia in the induction of renal hypertrophy. Am J Kidney Dis 17:650-3 |
| Golchini, K; Mackovic-Basic, M; Gharib, S A et al. (1990) Synthesis and characterization of a new fluorescent probe for measuring potassium. Am J Physiol 258:F438-43 |
| Golchini, K; Norman, J; Bohman, R et al. (1989) Induction of hypertrophy in cultured proximal tubule cells by extracellular NH4Cl. J Clin Invest 84:1767-79 |
| Fine, L G; Norman, J (1989) Cellular events in renal hypertrophy. Annu Rev Physiol 51:19-32 |
| Norman, J T; Bohman, R E; Fischmann, G et al. (1988) Patterns of mRNA expression during early cell growth differ in kidney epithelial cells destined to undergo compensatory hypertrophy versus regenerative hyperplasia. Proc Natl Acad Sci U S A 85:6768-72 |
