Endothelin-1 increases 2-arachidonoyl glycerol (2-AG) production in astrocytes.
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.
Walter
Lisa
L
Department of Pharmacology, University of Washington, Seattle, Washington, USA.
Stella
Nephi
N
D000818:Animals; D000831:Animals, Newborn; D001095:Arachidonic Acids / Q000378:metabolism*; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D001921:Brain / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D001930:Brain Injuries / Q000188:drug therapy / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D063388:Endocannabinoids; D019332:Endothelin-1 / Q000378:metabolism* / Q000494:pharmacology; D005989:Glycerides / Q000378:metabolism*; D051379:Mice; D019899:Paracrine Communication / Q000187:drug effects / Q000502:physiology; D043882:Receptors, Cannabinoid / Q000187:drug effects / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology*
D001095:Arachidonic Acids; D063388:Endocannabinoids; D019332:Endothelin-1; D005989:Glycerides; D043882:Receptors, Cannabinoid; C094503:glyceryl 2-arachidonate