Mp. Bos et al., DOWN-REGULATION AND DIFFERENTIAL RESTORATION OF CAMP RESPONSES UPON TRANSIENT PHORBOL ESTER TREATMENT OF PRIMARY OSTEOBLASTIC CELLS, Cellular signalling, 7(6), 1995, pp. 617-626
We studied cAMP responses induced by parathyroid hormone (PTH), prosta
glandin E(2) (PGE(2)) and forskolin in foetal rat calvariae-derived os
teoblastic cells after 24 h treatment with a protein kinase C (PKC) ac
tivating phorbol ester. After this treatment, meant to down-regulate P
KC activity, all tested cAMP responses were attenuated and were indeed
accompanied by a decline in PKC activity. PTH receptor affinity was n
ot altered and PTH receptor number was only slightly lowered after 24
h phorbol ester treatment. These results indicate that modulation of t
he cAMP responses by 24 h PMA treatment was mainly caused by a general
impairment of adenylyl cyclase activity. Removal of the phorbol ester
and subsequent culture for 2 days rendered the cells hyper-responsive
to PTH: the PTH-induced cAMP response was 2 to 3 times higher than in
control cells. Again no change in binding affinity of the PTH recepto
r was observed and receptor number was just 10% lower than in control
cells. The PGE(2)- and forskolin-induced cAMP responses were not highe
r than normal. So, transient phorbol ester treatment leads to a differ
ential, agonist-dependent restoration of the cAMP signalling system.