Previous studies have indicated an important role for the sympathetic nervous system in regulating renal sodium metabolism. Recently, evidence has been accumulating that dopaminergic activity may contribute significantly to this regulation. Our studies suggest that the contribution of dopamine to sodium metabolism differs from the neonate to the adult animal. As yet, it has not been determined whether these receptors are luminal or antiluminal, and where along the nephron (proximal convoluted tuble, loop of Henle, distal tubule, collecting duct) they are located. Moreover, the in vitro methods of characterizing dopamine receptors (radioligand binding and adenylate cyclase) and in vivo methods (effect on sodium excretion) have not been compared. The current proposal will examine these different issues. Dopamine receptors will be evaluated by 1) radioligand binding methods by measuring the specific binding of 3H-haloperidol in luminal and antiluminal membranes from control animals; 2) binding studies will also be performed in specific nephron segments obtained by microdissection; 3) adenylate cyclase will be measured in the same membranes studied by radioligand binding; 4) the effects of dopamine agonists and antagonists on fractional sodium excretion will be studied in intact animals. The dissociation constants obtained from the in vitro and in vivo studies will be compared. 5) To determine the role of dopamine on renal sodium metabolism, these receptors will also be characterized in developing and mature dogs on varied salt intakes; 6) The role of dopamine in sodium excretion will be further delineated from beta and alpha adrenergic effects by studying the consequences of dopamine blockade as well as alpha and beta blockade in the unilaterally denervated kidney model; 7) the locus of dopamine action on renal sodium transport will be further evaluated by proximal and distal tubular micropuncture studies. These studies should provide full characterization of renal tubular dopamine receptors by comparing the results of in vitro studies with in vivo studies and a clearer insight into the role of dopamine receptors in salt metabolism.
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