AJP - Endocrinology and Metabolism, Vol 262, Issue 1 E87-E95, Copyright © 1992 by American Physiological Society
Protein kinase C differentially modulates PTH- and PGE2-sensitive adenylate cyclase in osteoblast-like cells
A. M. Freyaldenhoven, G. E. Gutierrez, M. D. Lifschitz and M. S. Katz
Department of Medicine, University of Texas Health Science Center, San Antonio.
The effects of phorbol 12-myristate 13-acetate (PMA), a known activator of
protein kinase C, on receptor-mediated stimulation of adenylate cyclase
were evaluated in a rat osteosarcoma cell line (UMR-106) with the
osteoblast phenotype. Pretreatment of UMR-106 cells with PMA increased
parathyroid hormone (PTH)-stimulated adenylate cyclase activity and
inhibited prostaglandin E2 (PGE2)-responsive enzyme activity. In addition,
PMA enhanced enzyme activation by forskolin, which is thought to exert a
direct stimulatory action on the catalytic subunit of adenylate cyclase.
The regulatory effects of PMA were concentration dependent and of rapid
onset (less than or equal to 1 min). Treatment with PMA also resulted in
translocation of protein kinase C activity from the cytosol to the
particulate cell fraction. Pertussis toxin, which attenuates inhibition of
adenylate cyclase mediated by the inhibitory guanine nucleotide-binding
regulatory protein (Gi), augmented PTH-sensitive adenylate cyclase activity
and reduced the incremental increase in PTH response produced by PMA. The
results suggest that activation of protein kinase C increases
PTH-stimulated adenylate cyclase activity by actions on Gi and/or the
catalytic subunit and decreases PGE2 responsiveness by a mechanism
involving the PGE2 receptor.
