(-)-Delta9-tetrahydrocannabinol antagonizes the peripheral cannabinoid receptor-mediated inhibition of adenylyl cyclase.
M Bayewitch, M H Rhee, T Avidor-Reiss, Aviva Breuer, Raphael Mechoulam, Z Vogel
Journal of Biological Chemistry April 26, 1996 DOI: 10.1074/jbc.271.17.9902 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | In vitro receptor pharmacology study Peer reviewed |
|---|---|
| Population | Chinese hamster ovary cells and COS cells transfected with cannabinoid receptors |
| Intervention | (-)-Delta9-Tetrahydrocannabinol |
| Topics | Cannabis |
| Key points | (-)-Delta9-THC bound CB1 and CB2 receptors with similar affinity. It acted as an agonist at CB1, inhibiting adenylyl cyclase, but at CB2 it caused only a very slight inhibition and antagonized agonist-induced inhibition of adenylyl cyclase. The authors conclude that (-)-Delta9-THC is a weak antagonist for the CB2 receptor. |
Abstract
(-)-Delta9-Tetrahydrocannabinol ((-)-Delta9-THC) is the major active psychotropic component of the marijuana plant, Cannabis sativa. The membrane proteins that have been found to bind this material or its derivatives have been called the cannabinoid receptors. Two GTP-binding protein-coupled cannabinoid receptors have been cloned. CB1 or the neuronal cannabinoid receptor is found mostly in neuronal cells and tissues while CB2 or the peripheral cannabinoid receptor has been detected in spleen and in several cells of the immune system. It has previously been shown that activation of CB1 or CB2 receptors by cannabinoid agonists inhibits adenylyl cyclase activity. Utilizing Chinese hamster ovary cells and COS cells transfected with the cannabinoid receptors we report that (-)-Delta9-THC binds to both receptors with similar affinity. However, in contrast to its capacity to serve as an agonist for the CB1 receptor, (-)-Delta9-THC was only able to induce a very slight inhibition of adenylyl cyclase at the CB2 receptor. Morever, (-)-Delta9-THC antagonizes the agonist-induced inhibition of adenylyl cyclase mediated by CB2. Therefore, we conclude that (-)-Delta9-THC constitutes a weak antagonist for the CB2 receptor.
Comparable studies
Other preclinical and animal studies on cannabis, most cited first.
Citations in the library
Cited by 3
- Effect fingerprinting of new psychoactive substances (NPS): What can we learn from in vitro data? Pharmacology & Therapeutics February 1, 2018
- Similarities and differences upon binding of naturally occurring Δ9-tetrahydrocannabinol-derivatives to cannabinoid CB1 and CB2 receptors. Pharmacological Research December 2021
- The diverse CB1 and CB2 receptor pharmacology of three plant cannabinoids: delta9-tetrahydrocannabinol, cannabidiol and delta9-tetrahydrocannabivarin. British Journal of Pharmacology January 2008