The epoxy fatty acid pathway enhances cAMP in mammalian cells through multiple mechanisms

Prostaglandins Other Lipid Mediat. 2022 Oct:162:106662. doi: 10.1016/j.prostaglandins.2022.106662. Epub 2022 Jun 30.

Abstract

The cellular mechanism by which epoxy fatty acids (EpFA) improves disease status is not well characterized. Previous studies suggest the involvement of cellular receptors and cyclic AMP (cAMP). Herein, the action of EpFAs derived from linoleic acid (LA), arachidonic acid (ARA), and docosahexaenoic acid on cAMP levels was studied in multiple cell types to elucidate relationships between EpFAs, receptors and cells' origin. cAMP levels were enhanced in HEK293 and LLC-PK1 cells by EpFAs from LA and ARA. Using selective antagonists, the EpFA effects on cAMP levels appear dependent on the prostaglandin E2 receptor 2 (EP2) but not 4 (EP4). Human coronary artery smooth muscle cells responded similarly to the EpFAs. However, we were not able to show the involvement of any of the receptors tested in this cell type. The results pinpointed distinct cell lines and receptor subtypes that natively respond to EpFA.

Keywords: Cyclic AMP; Dihydroxyeicosatrienoic acid; EP2; Eicosanoid; Epoxyeicosatrienoic acid; Inflammation; Soluble epoxide hydrolase.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Arachidonic Acid
  • Cyclic AMP* / metabolism
  • Docosahexaenoic Acids
  • Fatty Acids
  • HEK293 Cells
  • Humans
  • Linoleic Acids
  • Mammals / metabolism
  • Prostaglandins
  • Receptors, Prostaglandin E, EP2 Subtype / metabolism
  • Receptors, Prostaglandin E, EP4 Subtype* / metabolism

Substances

  • Fatty Acids
  • Linoleic Acids
  • Prostaglandins
  • Receptors, Prostaglandin E, EP2 Subtype
  • Receptors, Prostaglandin E, EP4 Subtype
  • Docosahexaenoic Acids
  • Arachidonic Acid
  • Cyclic AMP