Synthetic tumor-derived human hypercalcemic factor exhibits parathyroid hormone-like vasorelaxation in renal arteries.
Synthetic human tumor hypercalcemic factor (1-34, hHF) was compared with parathyroid hormone (human sequence, 1-34; hPTH) for vasorelaxant activity in isolated rabbit renal artery segments. The hHF exhibited a potent (IC50 = 1.3 x 10(-9) M) and profound (98%) relaxation which was significantly greater in magnitude than that obtained for hPTH (IC50 = 4.5 x 10(-9) M; maximal relaxation = 78%). The relaxations to both peptides were concentration-dependent and not associated with changes in cyclic AMP levels. These results demonstrate a parathyroid hormone-like response, independent of adenylate cyclase activation, in isolated renal arteries. Renal vasodilation may be important for the effects on renal function shared by these two peptides.
Winquist
R J
RJ
Department of Pharmacology, Merck Sharp & Dohme Research Laboratories, West Point, PA 19486.
Baskin
E P
EP
Vlasuk
G P
GP
D000818:Animals; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D006801:Humans; D008297:Male; D008729:Methoxamine / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects*; D009126:Muscle Relaxation / Q000187:drug effects*; D009363:Neoplasm Proteins / Q000494:pharmacology*; D010281:Parathyroid Hormone / Q000494:pharmacology*; D044162:Parathyroid Hormone-Related Protein; D010446:Peptide Fragments / Q000494:pharmacology*; D011506:Proteins; D011817:Rabbits; D012077:Renal Artery / Q000187:drug effects / Q000502:physiology*
D009363:Neoplasm Proteins; D010281:Parathyroid Hormone; D044162:Parathyroid Hormone-Related Protein; D010446:Peptide Fragments; D011506:Proteins; C054296:parathyroid hormone-related protein (1-34); D005576:Colforsin; D000242:Cyclic AMP; D008729:Methoxamine