Abstract
The predominant psychotropic agent of the marihuana plant Cannabis sativa, Δ9-tetrahydrocannabinol, has a diversity of pharmacological effects in mammalian systems.1 Some of these indicate that cannabinoids are of potential utility in treating diverse human conditions such as inflammation, pain and nausea. In the last several years, the effects of cannabinoids have been shown to occur through receptor mediated in addition to receptor independent pathways.1 The rat neuronal cannabinoid receptor (CB1), cloned and se-quenced in 1990, is of structure typical of G-protein coupled receptors with seven transmembrane domains.2 Soon after the discovery of this receptor, its endogenous ligand, anandamide, was isolated and structurally defined.3 It was of surprise that such an uncomplicated substance, composed simply of arachidonic acid and ethanolamine subunits, should have such an important neurochemical role (figure 1). The in vitro and in vivo pharmacological actions of anandamide are comparable to those of Δ9-THC, and include inhibition of adenylate cyclase, inhibition of N-type Ca+2 channels, inhibition of locomotor activity, and production of hypothermia, antinociception, and catalepsy.1 Correspondingly, there is great interest in both the structure-activity relationships of this new class of neurochemical as well as the search for new agonists and antagonists of this receptor. Our interest is focused in these latter areas, with our two approaches being 1) the screening of natural product extracts from marine organisms for agents that bind with high affinity to the cannabinoid receptor, and 2) the use of the unusual fatty acid metabolizing systems of marine algae to make correspondingly unique analogs of anandamide. Our progress with these two approaches forms the basis of this report.
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© 1997 Springer Science+Business Media New York
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Gerwick, W.H., Wise, M.L., Soderstrom, K., Murray, T.F. (1997). Biosynthesis and Cannabinoid Receptor Affinity of the Novel Eicosanoid, Conjugated Triene Anandamide. In: Honn, K.V., Marnett, L.J., Nigam, S., Jones, R.L., Wong, P.YK. (eds) Eicosanoids and other Bioactive Lipids in Cancer, Inflammation, and Radiation Injury 3. Advances in Experimental Medicine and Biology, vol 407. Springer, Boston, MA. https://doi.org/10.1007/978-1-4899-1813-0_49
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DOI: https://doi.org/10.1007/978-1-4899-1813-0_49
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