title: Differential effects of parathyroid hormone responsive cultured human cells on biological activity of parathyroid hormone and parathyroid hormone inhibitory analogues.
abstract: We have employed parathyroid hormone (PTH) responsive human cells cultured from dermis or giant cell tumors of bone (GT) to evaluate the biological properties of a newly developed in vivo PTH inhibitor, [Tyr34]bPTH-(7-34)-amide (PTH-Inh). Short periods of incubation of cells from dermis or GT with maximal stimulatory concentrations of PTH in the presence of increasing concentrations of PTH-Inh resulted in a dose-dependent inhibition of the adenosine cyclic 3',5'-phosphate (cAMP) response (Ki = 3 X 10(-7) M and 4.2 X 10(-7) M for GT and dermal cells, respectively). In both cell cultures, PTH-Inh alone did not increase cAMP levels, and in desensitization experiments, preincubation with PTH-Inh alone did not desensitize cells to PTH. Hence, the analogue displayed no agonist properties. Unexpectedly, when PTH-Inh was incubated with dermal cells in the presence of PTH, the PTH-Inh failed to block desensitization, suggesting a loss of biological effectiveness of the inhibitor. When medium containing PTH-Inh alone was removed from dermal cells and tested for inhibition of the acute PTH response in untreated cells, there was apparent loss of inhibitory efficacy (t1/2 = 20 h). In contrast, incubation of native PTH or bPTH-(1-34) with cells did not affect the biological activity of these ligands. Unlike the dermal cells, the PTH-Inh did block desensitization to PTH in GT, and there was no loss of inhibitor efficacy when medium containing PTH-Inh was incubated with GT (48 h) and then tested in untreated cells.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.forename: S R
authors.initials: SR
authors.lastname: Goldring
authors.forename: M S
authors.initials: MS
authors.lastname: Roelke
authors.forename: F R
authors.initials: FR
authors.lastname: Bringhurst
authors.forename: M
authors.initials: M
authors.lastname: Rosenblatt
mesh_terms: D001681:Biological Assay; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000096:biosynthesis; D006801:Humans; D010281:Parathyroid Hormone / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D010281:Parathyroid Hormone; D010446:Peptide Fragments; C038040:parathyroid hormone (7-34)amide, Tyr(34)-; D000242:Cyclic AMP