Activators of protein kinase A decrease the levels of free arachidonic acid in osteoblasts via stimulation of phosphatidylcholine and phosphatidylethanolamine synthesis. Academic Article uri icon

Overview

abstract

  • In order to examine the role of protein kinase A (PKA) in the regulation of arachidonic acid availability, the interaction between cAMP agonists and the G protein activator AIF4- in their effects on phospholipid metabolism were measured in MC3T3-E1 osteoblasts. We show that forskolin and 8-brcAMP, activators of PKA, amplify the AIF4(-)-induced stimulation of phosphatidylinositol-specific phospholipase C (phosphatidylinositol inositolphosphohydrolase; EC 3.1.4.3), measured by the formation of [3H]inositol phosphates in prelabeled cells. However, the AIF4(-)-stimulated production of 1,2-diacylglycerols and the release of [3H]arachidonic acid ([3H]AA) were inhibited 50-75% by forskolin and 8-bromocAMP. Furthermore, pretreatment with PKA activators prevented much of the AIF4(-)-induced loss of [3H]AA from phosphatidylcholine and phosphatidylethanolamine in prelabeled osteoblasts. In addition, in the absence of AIF4-, forskolin was found to stimulate the incorporation of [3H]AA and [32P]orthophosphoric acid selectively into these two major phospholipids and selectively increased their mass. The effects of forskolin and 8-BrcAMP on the levels of free [3H]AA were completely reversed by pretreatment with the PKA inhibitor H-89. Therefore, our findings suggest that the activation of cAMP-dependent protein kinase can reduce the availability of free arachidonic acid for prostaglandin synthesis in osteoblast cells by stimulating its reesterification via phospholipid resynthesis.

publication date

  • February 1, 1998

Research

keywords

  • Arachidonic Acid
  • Cyclic AMP-Dependent Protein Kinases
  • Osteoblasts
  • Phosphatidylcholines
  • Phosphatidylethanolamines

Identity

Scopus Document Identifier

  • 0031885903

Digital Object Identifier (DOI)

  • 10.1016/s0952-3278(98)90155-7

PubMed ID

  • 9578154

Additional Document Info

volume

  • 58

issue

  • 2