Direct characterization of renal amino acid transport has been mainly restricted to the proximal convoluted tubule (S-1)(23,27,28). Amino acid transport studies (1,2,3,22) in the proximal straight tubule (S-2) have been few and no information is available on the late proximal straight tubules (S-3) handing of amino acids. In addition, it is not clear how many independent amino acids transport mechanisms exist along the proximal tubule and if some amino acids share transport mechanisms, or if the location of a shared mechanism is at the luminal membrane or basolateral membrane (11,12,28,32). This study is designed to directy answer these questions using the rabbit isolated perfused nephron. The transport of four amino acids will be studied in the S-1, S-2, and S-3 segments of the proximal tubule. The amino acids to be studied are arginine, aspartic acid, alanine and proline, each representing a proported amino acid transport system, namely, dibasic, acidic, neutral and imino, respectively. It will be determined if these amino acids represent different transport mechanisms in all three segments (S-1, S-2 and S-3) (3,31) of the proximal tubule as well as quantitate their transport characteristics J-max, K-m and leak (k) in each segment. Other amino acids that are reported to share transport mechanisms with the amino acid in this study will be tested to determine if the shared transport site is located at the entry step on the luminal membrane or exit step at basolateral membrane. In addition, it will be determined if the active site for transepithelial absorptive transport is located at the luminal or basolateral membrane. Uptake of amino acids by the basolateral membrane from peritubular fluid in the three segments of the proximal tubule will be examined. Basolateral sequestering of glycine has been observed by the principal investigator (3). If this is a general characteristic for the proximal straight tubule it could explain amino acid secretion in some pathological settings. Finally, all this information, namely, axial distribution of transport along the nephron (J-max, K-m, and k) and sites of amino acid interaction, will be incorporated into a model to explain the mechanisms in the nephron that reclaim nearly 100% of the filtered amino acids.
| Barfuss, D W; Ganapathy, V; Leibach, F H (1988) Evidence for active dipeptide transport in isolated proximal straight tubules. Am J Physiol 255:F177-81 |
