Aldosterone and dopamine receptors in the kidney: Sites for pharmacologic manipulation of renal function

The development of radio-ligands with a high specific activity has greatly facilitated the study of hormonal receptor systems. These receptor studies have given us insight into the actions of drugs already available and should be helpful in assessing potential drugs, both for their desired and undesired effects. The kidney is the most physiologically important end organ for some hormones (for example, aldosterone, antidiuretic hormone). In addition, some hormones with multiple actions have unique actions within the kidney (for example, parathyroid hormone and phosphate excretion). The kidney may also act as an end organ in a relatively subordinate role compared with a hormone's action elsewhere in the body (for example, glucocorticoids). Demonstration of a hormone receptor system within the kidney, as elsewhere, does not, by itself, imply any physiologic action of the ligand. Before allowing receptor studies to influence assessments of drugs, we need to evaluate carefully the receptor for the effector systems and their physiologic importance. By intentionally manipulating the hormone receptor systems, we can seek the desired effects and evaluate them. Problems arise in the kidney in discerning unintentional manipulation of receptor systems, otherwise known as side effects. This problem arises because of the kidneys' remarkable capability to adapt to a functional impairment with a minimal change in the internal environment [1]. The kidneys' ability to adapt to functional impairment is most easily demonstrated with progressive loss of renal function, where many aspects of homeostasis are achieved until late in the disease [1]. A similar adaptation in function can be seen with drug-mediated manipulation of a specific kidney function. For instance, in healthy people, the administration of diuretics of any type is hard to discern except in the early diuretic phase, for sodium and potassium balance are achieved rapidly with a minimal observable change in sodium or potassium homeostasis. Evaluation of drugs by receptor studies may guide in predicting likely undesired effects. In this paper, two topics will be discussed that, at first, may seem quite distinct but for which there does seem to be evidence for their interrelationship in both renal and extrarenal sites. The first is drug interaction with the aldosterone receptor, as an example of a hormone receptor system in which the kidney is the end organ of major physiologic importance. The second is the dopamine