Selective thick ascending limb and medullary collecting duct hyporesponsiveness to the vasopressin (AVP) stimulation of adenylate cyclase have been demonstrated respectively in the hypothyroid and potassium-depleted states. Both defects are associated with decreased or immpaired renal concentrating ability. Although these indirect techniques localize the site of dysfunciton along the nephron, little is known about the nature of the defect. The hyporesponsiveness can be the result of either decreased receptor number or affinity or alternatively to post-receptor events. Radioactive tracers for binding studies at the nephron level have either too low specific activity or no bioactivity.
The specific aim of this project is the direct measurement of AVP receptor distribution along the nephron in health and in states of abnormal water metabolism. To achieve this goal, a diversified radioimmunological approach will be adopted. This will include the use of highly sensitive AVP radioimmunoassary (RIA) techniques and the production of antireceptor antibodies. The RIA method will consist of the accurate measurement of AVP binding and its displacement by an AVP agonist which does not crossreact in the RIA. Antireceptor antibodies will be produced by using the monoclonal technology as well as the antidiotypic approach. THe results should help elucidate the pathophysiology of abnormal functional response to AVP in states of abnormal water balance and provide a probe for the further study of receptor function and regulations.
| Durr, J A (1993) Determination of specific activity of labeled ligands by nonlinear regression analysis. Am J Physiol 265:E728-35 |
| Durr, J A; Hoffman, W H; Sklar, A H et al. (1992) Correlates of brain edema in uncontrolled IDDM. Diabetes 41:627-32 |
| Durr, J A; Hensen, J; Schrier, R W (1992) High specific activity 125I- and 35S-labeled vasopressin analogues with high affinity for the V1 and V2 vasopressin isoreceptors. J Biol Chem 267:18453-8 |
| Durr, J A; Miller, N L; Alfrey, A C (1990) Lithium clearance derived from the natural trace blood and urine lithium levels. Kidney Int Suppl 28:S58-62 |
| Durr, J A; Hoggard, J G; Hunt, J M et al. (1987) Diabetes insipidus in pregnancy associated with abnormally high circulating vasopressinase activity. N Engl J Med 316:1070-4 |
