Elsevier

Life Sciences

Volume 35, Issue 17, 22 October 1984, Pages 1803-1810
Life Sciences

Inhibition of neuroblastoma adenylate cyclase by cannabinoid and nantradol compounds

https://doi.org/10.1016/0024-3205(84)90278-9Get rights and content

Abstract

This study was undertaken to ascertain the effects of cannabinoid drugs on prostanoid-stimulated adenylate cyclase in neuroblastoma cells. This report demonstrates that Δ9-tetrahydrocannabinol (THC) and levonantradol could decrease initial rate cyclic AMP accumulation in response to prostacyclin in intact cells. Basal accumulation was also diminished. Prostanoid-stimulated adenylate cyclase in a membrane preparation from these cells was inhibited by cannabinoid and nantradol compounds. However, this inhibition was not competitive with prostaglandin E1 or prostacyclin. Further, inhibition was also observed when the enzyme was stimulated by peptide hormones at the secretin receptor. In contrast, enzyme activated by NaF was not inhibited by cannabinoid compounds. Cyclic AMP phosphodiesterase activity in subcellular fractions was unaltered by these agents. These data demonstrate that cannabinoid and nantradol compounds decrease cyclic AMP accumulation in neuronally derived cells, and that this results from an inhibition of basal and hormone-stimulated adenylate cyclase activity.

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    Citation Excerpt :

    Following identification of THC, several other pivotal events drove the discovery in humans and animals of a ubiquitous endogenous system, coined the endocannabinoid system (ECS), that mediates the effects of Cannabis and cannabinoids. These events included evidence that THC actions are stereospecific (Mechoulam et al., 1988), a tell-tale sign of high-affinity receptor interactions, and the demonstration that cannabinoids signal in cells via a receptor-mediated decrease in adenylyl cyclase (Howlett, 1984). Synthesis of high-affinity synthetic cannabinoids contributed to the cloning of cannabinoid 1 receptor and subsequent analysis of receptor distribution and pharmacology (Gerard, Mollereau, Vassart, & Parmentier, 1991; Matsuda, Lolait, Brownstein, Young, & Bonner, 1990).

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