Biologic activities of parathyroid hormone (1-34) and parathyroid hormone-related peptide (1-34) in isolated perfused rat femur.
Parathyroid hormone-related peptide (PTHrP) has substantial homology with both human and rat parathyroid hormone (66% and 73%, respectively) in the first 15 amino acids. PTHrP (1-34) stimulates cyclic adenosine monophosphate (cAMP) release in bone and kidney, and these effects are felt to occur through interaction with the parathyroid hormone (PTH) receptor. Differences in the biologic potency between rat PTH(1-34) and human PTH(1-34)--and between PTHrP and PTH--have been described in a variety of experimental systems. In this study, we compared the bioactivity of these three amino-terminal synthetic fragments on the stimulation of cAMP formation in an isolated perfused rat femur preparation. Dose-response experiments demonstrated that PTHrP(1-34) was more potent in stimulating cAMP release than human PTH(1-34), whereas PTHrP(1-34) and rat PTH(1-34) were equipotent. Despite the fact that the extraction of immunoreactive rat PTH(1-34) and human PTH(1-34) was the same, rat PTH(1-34) was more potent in stimulating adenylate cyclase activity than human PTH(1-34). These data show that the isolated perfused rat femur preparation is an effective method for evaluation of the effects of PTH and PTHrP. Despite significant structural differences in the binding domain between rat PTH(1-34) and PTHrP(1-34), the effects of rat PTH(1-34) and PTHrP(1-34) are similar. Because the structure of rat PTHrP(1-34) and human PTHrP(1-34) are identical, and because it is desirable to utilize homologous systems to study the potency and effects of test peptides, it would appear that rat PTH(1-34) is the most appropriate peptide for comparison with PTHrP in rat-based experimental systems.
Lopez-Hilker
S
S
Department of Medicine, Washington University School of Medicine, St. Louis, MO.
Martin
K J
KJ
Sugimoto
T
T
Slatopolsky
E
E
D000595:Amino Acid Sequence; D000818:Animals; D001842:Bone and Bones / Q000187:drug effects / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005269:Femur; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D008969:Molecular Sequence Data; D010281:Parathyroid Hormone / Q000378:metabolism / Q000494:pharmacology*; D044162:Parathyroid Hormone-Related Protein; D010446:Peptide Fragments / Q000378:metabolism / Q000494:pharmacology*; D010477:Perfusion; D011506:Proteins / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012689:Sequence Homology, Nucleic Acid; D019379:Teriparatide
D010281:Parathyroid Hormone; D044162:Parathyroid Hormone-Related Protein; D010446:Peptide Fragments; D011506:Proteins; D019379:Teriparatide; C054296:parathyroid hormone-related protein (1-34); D000242:Cyclic AMP