Publication Date:
1987-12-11
Description:
Peptides corresponding to the amino-terminal region of the parathyroid hormone-related protein (PTHrP) of humoral hypercalcemia of malignancy were synthesized. A 34-amino acid peptide, PTHrP(1-34), was two to four times more potent than bovine or human PTH(1-34) in bioassays promoting the formation of adenosine 3',5'-monophosphate (cAMP) and plasminogen activator activity in osteogenic sarcoma cells and adenylate cyclase activity in chick kidney membranes. Like parathyroid hormone itself, in which the activity resides in the first 34 residues, PTHrP peptides of less than 30 residues from the amino terminus showed substantially reduced activity. PTHrP(1-34) had only 6% of the potency of bovine PTH(1-34) in promoting bone resorption in vitro. PTHrP(1-34) strongly promoted the excretion of cAMP and phosphorus and reduced the excretion of calcium in the isolated, perfused rat kidney consistent with the symptoms seen in malignant hypercalcemia.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kemp, B E -- Moseley, J M -- Rodda, C P -- Ebeling, P R -- Wettenhall, R E -- Stapleton, D -- Diefenbach-Jagger, H -- Ure, F -- Michelangeli, V P -- Simmons, H A -- New York, N.Y. -- Science. 1987 Dec 11;238(4833):1568-70.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉University of Melbourne, Department of Medicine, Repatriation General Hospital, Heidelberg, Victoria, Australia.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/3685995" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Bone Resorption/*drug effects
;
Bone and Bones/metabolism
;
Calcium/metabolism
;
Cattle
;
Cells, Cultured
;
Humans
;
Hypercalcemia/etiology
;
Neoplasms/*physiopathology
;
Parathyroid Hormone/*pharmacology/physiology
;
Peptide Fragments/*pharmacology/physiology
;
Structure-Activity Relationship
;
Teriparatide
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
