Interspecies comparison of renal cortical receptors for parathyroid hormone and parathyroid hormone-related protein

Journal Article · Fri Mar 01 00:00:00 EST 1991 · Journal of Bone and Mineral Research; (USA)

DOI:https://doi.org/10.1002/jbmr.5650060310· OSTI ID:5760214

Orloff, J J; Goumas, D; Wu, T L; Stewart, A F ^[1]

---

1. West Haven Veterans Administration Medical Center, CT (USA)

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 of 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 ({sup 125}I)(Tyr36)hPTHrP-(1-36)NH{sub 2} binding to rat RCM by bPTH-(1-34) and (Tyr36)hPTHrP-(1-36)NH{sub 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 cross-linking 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.

• OSTI ID: 5760214
• Journal Information: Journal of Bone and Mineral Research; (USA), Vol. 6:3; ISSN 0884-0431
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
CYCLASES
ENZYME ACTIVITY
PARATHORMONE
RECEPTORS
SPECIFICITY
BIOCHEMICAL REACTION KINETICS
COMPARATIVE EVALUATIONS
DOGS
GENETIC VARIABILITY
IODINE 125
KIDNEYS
MAN
PHOTOCHEMISTRY
PROTEINS
RATS
SKELETON
TRACER TECHNIQUES
ANIMALS
BETA DECAY RADIOISOTOPES
BIOLOGICAL VARIABILITY
BODY
CHEMISTRY
DAYS LIVING RADIOISOTOPES
ELECTRON CAPTURE RADIOISOTOPES
ENZYMES
EVALUATION
HORMONES
INTERMEDIATE MASS NUCLEI
INTERNAL CONVERSION RADIOISOTOPES
IODINE ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
KINETICS
LYASES
MAMMALS
MEMBRANE PROTEINS
NUCLEI
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
ORGANS
PEPTIDE HORMONES
PRIMATES
RADIOISOTOPES
REACTION KINETICS
RODENTS
VERTEBRATES
550201* - Biochemistry- Tracer Techniques