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Formation and inactivation of endogenous cannabinoid anandamide in central neurons
Open accessAbstract
ANANDAMIDE (N-arachidonoyl-ethanolamine) was recently identified as a brain arachidonate derivative that binds to and activates cannabinoid receptors14, yet the mechanisms underlying formation, release and inactivation of this putative messenger molecule are still unclear. Here we report that anandamide is produced in and released from cultured brain neurons in a calcium ion-dependent manner when the neurons are stimulated with membrane-depolarizing agents. Anandamide formation occurs through phos-phodiesterase-mediated cleavage of a novel phospholipid precursor, N-arachidonoyl-phosphatidylethanolamine. A similar mechanism also governs the formation of a family of anandamide congeners, whose possible roles in neuronal signalling remain unknown. Our results and those of others5,6indicate therefore that multiple biochemical pathways may participate in anandamide formation in brain tissue. The life span of extracellular anandamide is limited by a rapid and selective process of cellular uptake, which is accompanied by hydrolytic degradation to ethanolamine and arachidonate. Our results thus strongly support the proposed role of anandamide as an endogenous neuronal messenger.
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Cited by
The Endocannabinoid System as an Emerging Target of Pharmacotherapy
Pacher, P., Bátkai, S., & Kunos, G. (2006) · Pharmacological Reviews · doi:10.1124/pr.58.3.2 · Cited by 2,077
The molecular logic of endocannabinoid signalling
Piomelli, D. (2003) · Nature Reviews Neuroscience · doi:10.1038/nrn1247 · Cited by 1,957
Self-citationEndogenous cannabinoids mediate retrograde signalling at hippocampal synapses
Wilson, R. I., & Nicoll, R. A. (2001) · Nature · doi:10.1038/35069076 · Cited by 1,607
Leptin-regulated endocannabinoids are involved in maintaining food intake
Di Marzo, V., Goparaju, S. K., Wang, L., Liu, J., Bátkai, S., Járai, Z., Fezza, F., Miura, G. I., Palmiter, R. D., Sugiura, T., et al. (2001) · Nature · doi:10.1038/35071088 · Cited by 1,559
Self-citationA second endogenous cannabinoid that modulates long-term potentiation
Stella, N., Schweitzer, P., & Piomelli, D. (1997) · Nature · doi:10.1038/42015 · Cited by 1,496
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Metadata
- Authors
- Di Marzo, V., Fontana, A., Cadas, H., Schinelli, S., Cimino, G., Schwartz, J.-C., & Piomelli, D.
- Venue
- Nature
- Published
- 1994-12
- Volume
- 372
- Issue
- 6507
- Pages
- 686-691
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2083371696
- Cited by
- 1,587
- References
- 0
- FWCI
- 32.22
- Type
- journal article
- Language
- en
- Open access
- green
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- Di Marzo, V., Fontana, A., Cadas, H., Schinelli, S., Cimino, G., Schwartz, J.-C., & Piomelli, D. (1994). Formation and inactivation of endogenous cannabinoid anandamide in central neurons. Nature. https://doi.org/10.1038/372686a0
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