A 7-34 analog of the parathyroid hormone-related protein has potent antagonist and partial agonist activity in vivo.
The biological properties of a new synthetic analog of parathyroid hormone-related protein [PTHrP-(7-34)NH2] were examined in vivo using a well characterized thyroparathyroidectomized (TPTX) rat model. The phosphaturic and urine cyclic AMP response induced by infusion of PTHrP-(1-34)NH2 (0.16 nmol/h) was inhibited by 70% (P less than 0.01, n = 6) by co-infusion of PTHrP-(7-34)NH2 at a 10-fold molar excess (1.6 nmol/h). The 7-34 PTHrP analog also antagonized the PTHrP-(1-34)NH2-induced hypercalcemia and rises in blood 1,25-dihydroxyvitamin D concentrations. However, when infused alone at a higher dose rate (8 nmol/h), PTHrP-(7-34)NH2 displayed significant PTH agonist activity. This profile contrasts to that of [Tyr-34]bPTH-(7-34)NH2 which is comparatively less potent (10-20-fold) with respect to its antagonist activity but has no appreciable agonist activity in vivo.
Horiuchi
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Bone Center/Division of Endocrinology, Cedars-Sinai Medical Center/UCLA School of Medicine.
Hongo
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T
Clemens
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TL
D000818:Animals; D002117:Calcitriol / Q000097:blood; D002118:Calcium / Q000097:blood; D000242:Cyclic AMP / Q000652:urine; D006934:Hypercalcemia / Q000139:chemically induced; D008297:Male; D010281:Parathyroid Hormone / Q000494:pharmacology; D044162:Parathyroid Hormone-Related Protein; D016105:Parathyroidectomy; D010446:Peptide Fragments / Q000494:pharmacology; D010710:Phosphates / Q000652:urine; D011506:Proteins / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013965:Thyroidectomy
D010281:Parathyroid Hormone; D044162:Parathyroid Hormone-Related Protein; D010446:Peptide Fragments; D010710:Phosphates; D011506:Proteins; C038040:parathyroid hormone (7-34)amide, Tyr(34)-; D000242:Cyclic AMP; D002117:Calcitriol; D002118:Calcium