Protein kinase C differentially modulates PTH- and PGE2-sensitive adenylate cyclase in osteoblast-like cells

A. M. Freyaldenhoven, G. E. Gutierrez, M. D. Lifschitz, Michael S Katz

Research output: Contribution to journalArticlepeer-review

20 Scopus citations


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 though 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 (≤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 (G(i)), 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 G(i) and/or the catalytic subunit and decreases PGE2 responsiveness by a mechanism involving the PGE2 receptor.

Original languageEnglish (US)
Pages (from-to)E87-E95
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Issue number1 25-1
StatePublished - Jan 1 1992


  • G proteins
  • Pertussis toxin
  • Phorbol ester

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Physiology (medical)


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