Endothelin-1 increases 2-arachidonoyl glycerol (2-AG) production in astrocytes

Glia. 2003 Oct;44(1):85-90. doi: 10.1002/glia.10270.


Astrocytes play an important role in neuroprotective responses. Recent studies indicate that endothelin-1, a neuropeptide upregulated during brain injury, increases levels of the endocannabinoid anandamide, a lipid with neuroprotective properties, in astrocytes in primary cultures. However, whether this neuropeptide also alters levels of 2-arachidonoyl glycerol (2-AG), the most abundant endocannabinoid in the CNS, in astrocytes remains unknown. In addition, 2-AG levels in astrocytes have never been measured. In this report we use chemical ionization gas chromatography/mass spectrometry to quantify picomole amounts of 2-AG in primary cultures of mouse astrocytes. We also demonstrate that endothelin-1 increases 2-AG production by 5-fold in these cells, a response that requires extracellular calcium and endothelin-1(A) receptor engagement. Immunocytochemistry showed that although cultured mouse neurons and microglia express cannabinoid receptors, cultured astrocytes do not. The data suggest that endothelin-1 modulates 2-AG production in astrocytes and that this endocannabinoid may participate in paracrine signaling toward neurons and microglia.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Animals, Newborn
  • Arachidonic Acids / metabolism*
  • Astrocytes / cytology
  • Astrocytes / drug effects
  • Astrocytes / metabolism*
  • Brain / cytology
  • Brain / drug effects
  • Brain / metabolism*
  • Brain Injuries / drug therapy
  • Brain Injuries / metabolism*
  • Calcium Signaling / drug effects
  • Calcium Signaling / physiology
  • Cells, Cultured
  • Endocannabinoids
  • Endothelin-1 / metabolism*
  • Endothelin-1 / pharmacology
  • Glycerides / metabolism*
  • Mice
  • Paracrine Communication / drug effects
  • Paracrine Communication / physiology
  • Receptors, Cannabinoid / drug effects
  • Receptors, Cannabinoid / metabolism
  • Up-Regulation / drug effects
  • Up-Regulation / physiology*


  • Arachidonic Acids
  • Endocannabinoids
  • Endothelin-1
  • Glycerides
  • Receptors, Cannabinoid
  • glyceryl 2-arachidonate