Evidence for glomerular receptors for parathyroid hormone

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Abstract
Glomerular receptors for parathyroid hormone (PTH) were demonstrated by 2 techniques: direct binding studies of 3H-labeled 1-34 human parathyroid hormone (hPTH) and an indirect approach using 125I-labeled specific antibodies directed against either 1-34 human or 1-84 bovine PTH. Specificity of binding relies on the following: binding equilibrium was reached both at increasing incubation times and increasing PTH concentrations; 1-34 [3H]hPTH binding was inhibited by unlabeled hormone and its analogs but by neither unrelated peptides nor inactivated PTH; addition of an excess of unlabeled 1-34 hPTH at equilibrium produced release of the tritiated hormone from its receptors; 1-34 [3H]hPTH did not bind to nontarget tissues; there was a close relationship between 1-34 [3H]hPTH binding and adenylate cyclase stimulation by this tracer, both processes displaying similar KD values close to 10-7 M; the peptides which compete with 1-34 [3H]hPTH for its binding sites were potent stimulators of adenylate cyclase, whereas those without effect on PTH binding were also inactive on this enzyme. Nonspecific binding represented 20-33% of total binding. Binding was pH and temperature dependent, maximum binding being observed at pH 7.3 and 10.degree. C. Binding also increased with Ca concentration in the range 0.01-1 mM. The degradation rate of 1-34 [3H]hPTH was slow and allowed binding at equilibrium to be studied without correcting hormone concentrations. The effect of PTH on glomerular filtration rate may involve a direct interaction with PTH binding sites in the renal glomeruli.