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Interspecies comparison of renal cortical receptors for parathyroid hormone and parathyroid hormone‐related protein
Author(s) -
Orloff John J.,
Goumas Douglas,
Wu Terence L.,
Stewart Andrew F.
Publication year - 1991
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1002/jbmr.5650060310
Subject(s) - parathyroid hormone , cyclase , adenylate kinase , medicine , parathyroid hormone receptor , endocrinology , receptor , chemistry , parathyroid hormone related protein , hormone receptor , biochemistry , biology , calcium , cancer , breast cancer
Parathyroid hormone (PTH) and PTH‐related proteins (PTHrP) interact with a common receptor in rat bone cells and in canine renal membranes with similar affinity, but PTHrP are substantially less potent than PTH in stimulating adenylate cyclase in canine renal membranes; in contrast, PTH and PTHrP are equipotent in stimulating adenylate cyclase in rat bone cells. This discrepancy has been largely viewed as reflecting differences in the relative efficiency of signal transduction for PTHrP between bone and kidney assay systems. To test the alternative (but not mutually exclusive) hypothesis that these differences could reflect interspecies differences in PTH receptors, we have characterized the bioactivity of amino‐terminal PTHrP and PTH in rat and human renal cortical membranes (RCM) and compared them to results we previously reported in canine RCM. The stability of PTH and PTHrP peptides under binding and adenylate cyclase assay conditions was greater than 80% for each species. Competitive inhibition of [ 125 I](Tyr 36 )hPTHrP‐(1–36)NH 2 binding to rat RCM by bPTH‐(1–34) and (Tyr 36 )hPTHrP‐(1–36)NH 2 yielded nearly identical binding dissociation constants (3.7 and 3.6 nM, respectively), and binding to human RCM demonstrated slightly greater potency for PTHrP (0.5 nM) than for PTH (0.9 nM). Similarly, adenylate cyclase stimulating activity was equivalent for the two peptides in rat RCM, but PTHrP was twofold more potent than PTH in human RCM. Covalent photoaffinity labeling of protease‐protected rat RCM yielded an apparent 80 kD receptor protein, and crosslinking of human RCM labeled an 85 kD receptor, indistinguishable in size from the canine renal PTH receptor. We conclude that rat, canine, and human renal cortical PTH receptors exhibit species specificity. The previously observed differences between rat bone cells and canine renal membranes in the efficiency of signal transduction by PTHrP may be explained, at least in part, by these species differences.