Cross-talk of parathyroid hormone-responsive dual signal transduction systems in osteoblastic osteosarcoma cells: Its role in PTH-induced homologous desensitization of intracellular calcium response
✍ Scribed by Toshitsugu Sugimoto; Kazuto Ikeda; Junichi Kano; Toru Yamaguchi; Masaaki Fukase; Kazuo Chihara
- Publisher
- John Wiley and Sons
- Year
- 1994
- Tongue
- English
- Weight
- 758 KB
- Volume
- 158
- Category
- Article
- ISSN
- 0021-9541
No coin nor oath required. For personal study only.
✦ Synopsis
The present study was designed to characterize the cross-talk of parathyroid hormone (PTH)-responsive dual signal transduction systems (CAMP-dependent protein kinase (PKA) and calcium/protein kinase C [PKCI) and its participation in PTH-induced homologous desensitization of intracellular calcium ([Caz']i) in osteoblastic UMR-106 cells. Although our recent study revealed that prolonged (more than 2 h) pretreatment with PKC-activating phorbol ester, phorbol 12myristate 13-acetate (PMA) significantly decreased the PTH-stimulated cAMP production, pretreatment with PMA and loph M) but not lo-" M 4alphaphorbol 12,13-didecanoate (PDD), incapable of activating PKC for 30 min significantly augmented TOp7 M hPTH-(I-34)-stimulated cAMP production. H-7 (50 uM), a PKC inhibitor, significantly antagonized this PMA-induced effect. Pretreatment with 1 Op6 M PMA for 30 min did not affect PTH receptor binding but significantly augmented a cAMP responsiveness to lop' M forskolin and 1 ug/ml cholera toxin. Pertussis toxin (0.5 ug/ml) did not affect the PMA-induced augmentation of the PTH-stimulated cAMP production. PTH caused a complete homologous desensitization of [Ca'+]i response within 30 min. Pretreatment with 10 M dibutyryl CAMP for 30 min and 6 h significantly reduced and completely blocked the PTH-induced increase in [Cazc]i, respectively. Pretreatment with I 0-4 M Sp-CAMPS, a direct PKA activator, for 30 min completely blocked the PTH-