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Endogenous cannabinoid receptor binding activity released from rat brain slices by depolarization
D M Evans1, J T Lake, M R Johnson
1Department of Pharmacological and Physiological Science, Saint Louis University School of Medicine, Missouri.
Summary
Researchers identified an endogenous cannabinoid receptor ligand released from nerve terminals. This release requires calcium and is modulated by specific inhibitors, acting as a receptor agonist.
Area of Science:
- Neuroscience
- Pharmacology
Background:
- An endogenous factor inhibiting cannabinoid receptor binding was previously identified.
- This factor is released from nerve terminals upon calcium influx.
Purpose of the Study:
- To investigate the release of the endogenous cannabinoid receptor ligand.
- To characterize the conditions and factors influencing its release and activity.
Main Methods:
- Depolarizing stimulus (75 mM K+) with extracellular calcium.
- Use of calcium channel blockers (verapamil, omega-conotoxin).
- Assay of cannabinoid receptor binding activity and adenylate cyclase inhibition.
Main Results:
- K+-evoked release of the endogenous ligand requires extracellular calcium.
- Calcium channel blockers reduced K+-evoked release.
- Peptidase inhibitors, specifically captopril and thiorphan, enhanced release.
- The released factor specifically binds to the cannabinoid receptor and acts as an agonist, inhibiting adenylate cyclase.
Conclusions:
- The endogenous cannabinoid receptor ligand is released from nerve terminals via a calcium-dependent mechanism.
- The released ligand functions as a cannabinoid receptor agonist with potential neuromodulatory roles.