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Electrically evoked acetylcholine release from hippocampal slices is inhibited by the cannabinoid receptor agonist, WIN 55212-2, and is potentiated by the cannabinoid antagonist, SR 141716A.
J Pharmacol Exp Ther. 1996 Jun; 277(3):1431-6.JP

Abstract

This study examined the effect of the cannabinoid receptor agonist, WIN 55212-2, on the electrically evoked release of [14C]acetylcholine (ACh) from superfused brain slices from the hippocampus, a region with a high density of cannabinoid receptors. A comparison was also made with [14C]ACh release from the nucleus accumbens, which has relatively fewer cannabinoid receptors. In the hippocampal slices, WIN 55212-2 produced a dose-dependent inhibition of [14C]ACh release, with an EC50 of 0.03 microM and a maximal inhibition of 81% at 1 microM. In the nucleus accumbens slices, WIN 55212-2 produced a weak inhibition of [14C]ACh release, which did not quite reach statistical significance. The inhibition of electrically evoked hippocampal [14C]ACh release by WIN 55212-2 could be prevented by the cannabinoid receptor antagonist, SR 141716A (EC50, 0.3-1.0 microM). In addition to antagonizing the effects of WIN 55212-2, SR 141716A alone produced a 2-fold potentiation of the electrically stimulated [14C]ACh release in this region (EC50, 0.1-0.3 microM). By contrast, in nucleus accumbens slices, no potentiation of the stimulated release of [14C]ACh release by SR 141716A was observed. Basal [14C]ACh release was unaffected by WIN 55212-2 or SR 141716A in either area. These results suggest that cannabinoid receptor activation can produce a strong inhibition of ACh release in the hippocampus. Furthermore, the potentiation of ACh release in the hippocampus by SR 141716A alone suggests either that this compound is an inverse agonist at cannabinoid receptors or it is antagonizing the actions of an endogenous ligand acting on these receptors.

Authors+Show Affiliations

Medical Department, Brookhaven National Laboratory, Upton, New York, USA.No affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

8667207

Citation

Gifford, A N., and C R. Ashby. "Electrically Evoked Acetylcholine Release From Hippocampal Slices Is Inhibited By the Cannabinoid Receptor Agonist, WIN 55212-2, and Is Potentiated By the Cannabinoid Antagonist, SR 141716A." The Journal of Pharmacology and Experimental Therapeutics, vol. 277, no. 3, 1996, pp. 1431-6.
Gifford AN, Ashby CR. Electrically evoked acetylcholine release from hippocampal slices is inhibited by the cannabinoid receptor agonist, WIN 55212-2, and is potentiated by the cannabinoid antagonist, SR 141716A. J Pharmacol Exp Ther. 1996;277(3):1431-6.
Gifford, A. N., & Ashby, C. R. (1996). Electrically evoked acetylcholine release from hippocampal slices is inhibited by the cannabinoid receptor agonist, WIN 55212-2, and is potentiated by the cannabinoid antagonist, SR 141716A. The Journal of Pharmacology and Experimental Therapeutics, 277(3), 1431-6.
Gifford AN, Ashby CR. Electrically Evoked Acetylcholine Release From Hippocampal Slices Is Inhibited By the Cannabinoid Receptor Agonist, WIN 55212-2, and Is Potentiated By the Cannabinoid Antagonist, SR 141716A. J Pharmacol Exp Ther. 1996;277(3):1431-6. PubMed PMID: 8667207.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Electrically evoked acetylcholine release from hippocampal slices is inhibited by the cannabinoid receptor agonist, WIN 55212-2, and is potentiated by the cannabinoid antagonist, SR 141716A. AU - Gifford,A N, AU - Ashby,C R,Jr PY - 1996/6/1/pubmed PY - 2001/3/28/medline PY - 1996/6/1/entrez SP - 1431 EP - 6 JF - The Journal of pharmacology and experimental therapeutics JO - J Pharmacol Exp Ther VL - 277 IS - 3 N2 - This study examined the effect of the cannabinoid receptor agonist, WIN 55212-2, on the electrically evoked release of [14C]acetylcholine (ACh) from superfused brain slices from the hippocampus, a region with a high density of cannabinoid receptors. A comparison was also made with [14C]ACh release from the nucleus accumbens, which has relatively fewer cannabinoid receptors. In the hippocampal slices, WIN 55212-2 produced a dose-dependent inhibition of [14C]ACh release, with an EC50 of 0.03 microM and a maximal inhibition of 81% at 1 microM. In the nucleus accumbens slices, WIN 55212-2 produced a weak inhibition of [14C]ACh release, which did not quite reach statistical significance. The inhibition of electrically evoked hippocampal [14C]ACh release by WIN 55212-2 could be prevented by the cannabinoid receptor antagonist, SR 141716A (EC50, 0.3-1.0 microM). In addition to antagonizing the effects of WIN 55212-2, SR 141716A alone produced a 2-fold potentiation of the electrically stimulated [14C]ACh release in this region (EC50, 0.1-0.3 microM). By contrast, in nucleus accumbens slices, no potentiation of the stimulated release of [14C]ACh release by SR 141716A was observed. Basal [14C]ACh release was unaffected by WIN 55212-2 or SR 141716A in either area. These results suggest that cannabinoid receptor activation can produce a strong inhibition of ACh release in the hippocampus. Furthermore, the potentiation of ACh release in the hippocampus by SR 141716A alone suggests either that this compound is an inverse agonist at cannabinoid receptors or it is antagonizing the actions of an endogenous ligand acting on these receptors. SN - 0022-3565 UR - https://www.unboundmedicine.com/medline/citation/8667207/Electrically_evoked_acetylcholine_release_from_hippocampal_slices_is_inhibited_by_the_cannabinoid_receptor_agonist_WIN_55212_2_and_is_potentiated_by_the_cannabinoid_antagonist_SR_141716A_ L2 - https://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=8667207 DB - PRIME DP - Unbound Medicine ER -