Crosstalk Between cAMP and Phosphoinositide System in Signal Transduction Pathways Through TSH Receptor / 대한내분비학회지
Journal of Korean Society of Endocrinology
; : 404-413, 2003.
Article
in Ko
| WPRIM
| ID: wpr-187346
Responsible library:
WPRO
ABSTRACT
BACKGROUND: TSH stimulates both the adenyl cyclase and phospholipase C (PLC) pathways by binding to a single cell surface receptor that is coupled to G protein, and we examined crosstalk between these two signaling pathways. METHODS: FRTL-5 rat thyroid cells were grown in 6H medium, then incubated with 5H medium before the stimulation. Then cells were incubated for 24 hours with 5H mix containing 1 mCi/L myo-(2-N-3H) inositol. After pretreatment of 100 microM Rp-cAMP, 100 microM forskolin, 50 nM staurosporine, or 100 nM PMA (phorbol-12-myristate-13-acetate), TSH were added in different experiments. After 30 min at 37 degrees C, cells were disrupted and IP formation was determined. RESULTS: Stimulation with 100 microU/mL TSH resulted in a 1.65 fold increase in IP generation. In pursuing the possibility that the two post-receptor events might be linked in some way, we examined the effect of exogenously administrated Rp-cAMP, protein kinase A antagonist, and forskolin, a direct stimulant of protein kinase A, on IP generation achieved at a dose of 100 microU/mL TSH. The pretreatment of 100 M Rp-cAMP at a concentration sufficient to inhibit protein kinase A enhanced TSH-induced IP production. This effect of Rp-cAMP was dose-dependent. Forskolin attenuatedTSH-stimulated increases in phosphatidylinositide turnover. PMA, a protein kinase C (PKC) activator and staurosporine, a PKC inhibitor did not affect TSH-induced IP generation. CONCLUSION: These data suggested that activation of adenylate cyclase/cAMP post-receptor signalling casacde, which results in the protien kinase A activation, has an inhibitory effect on IP turnover activated by TSH.
Key words
Full text:
1
Index:
WPRIM
Main subject:
Type C Phospholipases
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Phosphotransferases
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Thyroid Gland
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Receptors, Thyrotropin
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Colforsin
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Protein Kinase C
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Signal Transduction
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Adenylyl Cyclases
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Cyclic AMP-Dependent Protein Kinases
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Staurosporine
Limits:
Animals
Language:
Ko
Journal:
Journal of Korean Society of Endocrinology
Year:
2003
Type:
Article