Anandamide- and delta9-tetrahydrocannabinol-evoked arachidonic acid mobilization and blockade by SR141716A [N-(Piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4 -methyl-1H-pyrazole-3-carboximide hydrochloride].
A C Shivachar, B R Martin, E F Ellis
Biochemical Pharmacology March 8, 1996 DOI: 10.1016/s0006-2952(95)02248-1 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | In vitro cell culture study Peer reviewed |
|---|---|
| Population | Primary cultures of rat brain cortical astrocytes |
| Interventions | Anandamide delta9-tetrahydrocannabinol (delta9-THC) thimerosal phenylmethylsulfonyl fluoride SR141716A |
| Topics | Cannabis |
| Key points | Anandamide and delta9-THC stimulated time- and concentration-dependent arachidonic acid release from rat cortical astrocytes in the presence, but not absence, of thimerosal. The release was pertussis toxin-sensitive and blocked by the cannabinoid antagonist SR141716A, suggesting a receptor-mediated pathway; anandamide's effect matched equimolar delta9-THC, and amidohydrolase degradation of anandamide was negligible. |
Abstract
The purpose of this study was to investigate whether anandamide induces cannabimimetic responses, mainly mobilization of arachidonic acid, in primary cultures of rat brain cortical astrocytes. Confluent monolayer cultures of astrocytes, prelabeled with [3H]arachidonic acid, were incubated with anandamide or delta9-tetrahydrocannabinol (delta9-THC) in the presence or absence of thimerosal, a fatty acid acyl CoA transferase inhibitor and phenylmethylsulfonyl fluoride, an amidohydrolase inhibitor. Anandamide and delta9-THC induced a time- and concentration-dependent release of arachidonic acid in the presence, but not in the absence, of thimerosal. Anandamide- and delta9-THC-stimulated arachidonic acid release was pertussis toxin-sensitive, indicating a receptor/G-protein involvement. A novel and selective cannabinoid receptor antagonist, SR141716A [N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4- methyl-1H-pyrazole-3-carboximide hydrochloride], blocked the arachidonic acid release, suggesting a cannabinoid receptor-mediated pathway. In astrocytes, the magnitude of anandamide-induced arachidonic acid release was equal to that released by equimolar concentrations of delta9-THC. Furthermore, direct assay of amidohydrolase activity indicated that degradation of anandamide into arachidonic acid and ethanolamine was negligible in cortical astrocytes. Our results suggest that anandamide stimulates receptor-mediated release of arachidonic acid, and the receptor may be the cannabinoid receptor. Astrocytes, containing a cannabinoid receptor and lower or negligible amidohydrolase activity, may be an important brain cell model in which to study the cannabimimetic effects of anandamide at a cellular and molecular level.
Comparable studies
Other preclinical and animal studies on cannabis, most cited first.