Bidirectional modulation of parathyroid hormone-responsive adenylyl cyclase by protein kinase C

A. M. Kitten, T. K. Hymer, M. S. Katz

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

The temporal pattern with which phorbol 12-myristate 13-acetate (PMA), an activator of protein kinase C (PKC), modulates parathyroid hormone (PTH)- responsive adenylyl cyclase (AC) was evaluated in a clonal osteoblast-like cell line (UMR-106). Brief (≤ 1 h) exposure of UMR-106 cells to PMA enhanced PTH simulation of AC, whereas more prolonged PMA treatment decreased the PTH response, with maximum inhibition occurring at ≤ 6 h. PMA treatment also resulted in initial activation followed by downregulation of PKC. Exposure of cells to 1,2-dioctanoyl-sn-glycerol, which activated but did not downregulate PKC, resulted in bidirectional modulation of PTH-responsive AC identical to that produced by PMA. Prolonged PMA exposure decreased PTH receptor number, as determined by radioligand binding studies, and reduced PTH receptor mRNA levels, assessed by Northern blot analysis. Forskolin activation of the catalytic subunit of AC was also decreased after prolonged PMA treatment. The results suggest that activation of PKC sequentially stimulates and then inhibits PTH responsiveness. Inhibition of the PTH response occurs by PKC actions exerted on the PTH receptor and the AC catalytic subunit.

Original languageEnglish (US)
Pages (from-to)E897-E904
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume266
Issue number6 29-6
StatePublished - Jan 1 1994

Keywords

  • G proteins
  • diacylglycerol
  • osteoblast
  • parathyroid hormone receptor
  • phorbol ester

ASJC Scopus subject areas

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

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