Synthetic parathyroid hormone-like protein-(1-74): biochemical and physiological characterization.
PTH-like protein-(1-74) [PTHLP-(1-74)] was synthesized and purified. On the basis of chromatographic criteria and amino acid composition of the full-length peptide, direct amino acid sequencing of the N-terminus, and amino acid composition and internal sequence of proteolytic fragments of PTHLP-(1-74), the synthetic peptide appears to be of high quality and purity. Physiological comparison of PTHLP-(1-74) to [Tyr36]-PTHLP-(1-36) amide and bovine (b) PTH-(1-34) indicates that all three peptides are of equivalent potency in the fetal rat long bone and rat osteosarcoma 17/2.8 adenylate cyclase assays. However, as in earlier studies with native and N-terminal PTHLPs, PTHLP-(1-74) is considerably less potent (2%) in stimulating the canine renal cortical adenylate cyclase assay than is bPTH-(1-34). Further, PTHLP-(1-74) displayed only 12% of the activity of bPTH-(1-34) in inducing hypercalcemia when infused into rats in vivo. These studies support the possibility that subclasses of PTH receptors or varying PTH- and PTHLP-signalling transduction mechanisms may exist. In addition, they emphasize the need to precisely define the naturally occurring secretory and circulating species of this novel class of peptide hormones.
Stewart
A F
AF
Division of Endocrinology, West Haven Veterans Administration Medical Center, Connecticut 06516.
Elliot
J
J
Burtis
W J
WJ
Wu
T
T
Insogna
K L
KL
D000262:Adenylyl Cyclases / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001862:Bone Resorption / Q000187:drug effects; D002118:Calcium / Q000097:blood; D004285:Dogs; D007672:Kidney Cortex / Q000201:enzymology; D008969:Molecular Sequence Data; D010281:Parathyroid Hormone / Q000494:pharmacology; D044162:Parathyroid Hormone-Related Protein; D010446:Peptide Fragments / Q000138:chemical synthesis* / Q000494:pharmacology; D011506:Proteins / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats; D013329:Structure-Activity Relationship; D019379:Teriparatide
D010281:Parathyroid Hormone; D044162:Parathyroid Hormone-Related Protein; D010446:Peptide Fragments; D011506:Proteins; D019379:Teriparatide; C065306:parathyroid hormone-related protein (1-36), TyrNH2(36)-; C065305:parathyroid hormone-related protein (1-74); D000262:Adenylyl Cyclases; D002118:Calcium