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Anandamide and NADA bi-directionally modulate presynaptic Ca2+ levels and transmitter release in the hippocampus.
Br J Pharmacol. 2007 Jun; 151(4):551-63.BJ

Abstract

BACKGROUND AND PURPOSE

Inhibitory CB(1) cannabinoid receptors and excitatory TRPV(1) vanilloid receptors are abundant in the hippocampus. We tested if two known hybrid endocannabinoid/endovanilloid substances, N-arachidonoyl-dopamine (NADA) and anandamide (AEA), presynapticaly increased or decreased intracellular calcium level ([Ca(2+)](i)) and GABA and glutamate release in the hippocampus.

EXPERIMENTAL APPROACH

Resting and K(+)-evoked levels of [Ca(2+)](i) and the release of [(3)H]GABA and [(3)H]glutamate were measured in rat hippocampal nerve terminals.

KEY RESULTS

NADA and AEA per se triggered a rise of [Ca(2+)](i) and the release of both transmitters in a concentration- and external Ca(2+)-dependent fashion, but independently of TRPV(1), CB(1), CB(2), or dopamine receptors, arachidonate-regulated Ca(2+)-currents, intracellular Ca(2+) stores, and fatty acid metabolism. AEA was recently reported to block TASK-3 potassium channels thereby depolarizing membranes. Common inhibitors of TASK-3, Zn(2+), Ruthenium Red, and low pH mimicked the excitatory effects of AEA and NADA, suggesting that their effects on [Ca(2+)](i) and transmitter levels may be attributable to membrane depolarization upon TASK-3 blockade. The K(+)-evoked Ca(2+) entry and Ca(2+)-dependent transmitter release were inhibited by nanomolar concentrations of the CB(1) receptor agonist WIN55212-2; this action was sensitive to the selective CB(1) receptor antagonist AM251. However, in the low micromolar range, WIN55212-2, NADA and AEA inhibited the K(+)-evoked Ca(2+) entry and transmitter release independently of CB(1) receptors, possibly through direct Ca(2+) channel blockade.

CONCLUSIONS AND IMPLICATIONS

We report here for hybrid endocannabinoid/endovanilloid ligands novel dual functions which were qualitatively similar to activation of CB(1) or TRPV(1) receptors, but were mediated through interactions with different targets.

Authors+Show Affiliations

Center for Neurosciences of Coimbra, University of Coimbra, Coimbra, Portugal. akofalvi@yahoo.comNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

17435795

Citation

Köfalvi, A, et al. "Anandamide and NADA Bi-directionally Modulate Presynaptic Ca2+ Levels and Transmitter Release in the Hippocampus." British Journal of Pharmacology, vol. 151, no. 4, 2007, pp. 551-63.
Köfalvi A, Pereira MF, Rebola N, et al. Anandamide and NADA bi-directionally modulate presynaptic Ca2+ levels and transmitter release in the hippocampus. Br J Pharmacol. 2007;151(4):551-63.
Köfalvi, A., Pereira, M. F., Rebola, N., Rodrigues, R. J., Oliveira, C. R., & Cunha, R. A. (2007). Anandamide and NADA bi-directionally modulate presynaptic Ca2+ levels and transmitter release in the hippocampus. British Journal of Pharmacology, 151(4), 551-63.
Köfalvi A, et al. Anandamide and NADA Bi-directionally Modulate Presynaptic Ca2+ Levels and Transmitter Release in the Hippocampus. Br J Pharmacol. 2007;151(4):551-63. PubMed PMID: 17435795.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Anandamide and NADA bi-directionally modulate presynaptic Ca2+ levels and transmitter release in the hippocampus. AU - Köfalvi,A, AU - Pereira,M F, AU - Rebola,N, AU - Rodrigues,R J, AU - Oliveira,C R, AU - Cunha,R A, Y1 - 2007/04/16/ PY - 2007/4/17/pubmed PY - 2007/8/8/medline PY - 2007/4/17/entrez SP - 551 EP - 63 JF - British journal of pharmacology JO - Br J Pharmacol VL - 151 IS - 4 N2 - BACKGROUND AND PURPOSE: Inhibitory CB(1) cannabinoid receptors and excitatory TRPV(1) vanilloid receptors are abundant in the hippocampus. We tested if two known hybrid endocannabinoid/endovanilloid substances, N-arachidonoyl-dopamine (NADA) and anandamide (AEA), presynapticaly increased or decreased intracellular calcium level ([Ca(2+)](i)) and GABA and glutamate release in the hippocampus. EXPERIMENTAL APPROACH: Resting and K(+)-evoked levels of [Ca(2+)](i) and the release of [(3)H]GABA and [(3)H]glutamate were measured in rat hippocampal nerve terminals. KEY RESULTS: NADA and AEA per se triggered a rise of [Ca(2+)](i) and the release of both transmitters in a concentration- and external Ca(2+)-dependent fashion, but independently of TRPV(1), CB(1), CB(2), or dopamine receptors, arachidonate-regulated Ca(2+)-currents, intracellular Ca(2+) stores, and fatty acid metabolism. AEA was recently reported to block TASK-3 potassium channels thereby depolarizing membranes. Common inhibitors of TASK-3, Zn(2+), Ruthenium Red, and low pH mimicked the excitatory effects of AEA and NADA, suggesting that their effects on [Ca(2+)](i) and transmitter levels may be attributable to membrane depolarization upon TASK-3 blockade. The K(+)-evoked Ca(2+) entry and Ca(2+)-dependent transmitter release were inhibited by nanomolar concentrations of the CB(1) receptor agonist WIN55212-2; this action was sensitive to the selective CB(1) receptor antagonist AM251. However, in the low micromolar range, WIN55212-2, NADA and AEA inhibited the K(+)-evoked Ca(2+) entry and transmitter release independently of CB(1) receptors, possibly through direct Ca(2+) channel blockade. CONCLUSIONS AND IMPLICATIONS: We report here for hybrid endocannabinoid/endovanilloid ligands novel dual functions which were qualitatively similar to activation of CB(1) or TRPV(1) receptors, but were mediated through interactions with different targets. SN - 0007-1188 UR - https://www.unboundmedicine.com/medline/citation/17435795/Anandamide_and_NADA_bi_directionally_modulate_presynaptic_Ca2+_levels_and_transmitter_release_in_the_hippocampus_ L2 - https://doi.org/10.1038/sj.bjp.0707252 DB - PRIME DP - Unbound Medicine ER -