Diterpenoids from caribbean gorgonians act as noncompetitive inhibitors of the nicotinic acetylcholine receptor

Eterović, Vesna A.; Hann, Richard M.; Ferchmin, P.A.; Rodrı́guez, Abimael D.; Li, Lian; Lee, Yung-Hui; McNamee, Mark G.

doi:10.1007/bf00735367

Cited by 21 publications

(22 citation statements)

References 16 publications

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“…1). These cembranoids inhibited agonist-induced currents through the embryonic mouse muscle AChR expressed in Xenopus oocytes with IC 50 s in the low μmolar range (Eterovic et al 1993a). EUAC was also shown to partially block agonist-induced currents through T. californica electric organ AChR expressed in oocytes (Eterovic et al 1993b).…”

Section: Mechanisms Of Cembranoid Actions On Nicotinic Receptorsmentioning

confidence: 99%

Actions of octocoral and tobacco cembranoids on nicotinic receptors

Ferchmin

Pagán

Ulrich

et al. 2009

Toxicon

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Nicotinic acetylcholine receptors (AChRs) are pentameric proteins that form agonist-gated cation channels through the plasma membrane. AChR agonists and antagonists are potential candidates for the treatment of neurodegenerative diseases. Cembranoids are naturally occurring diterpenoids that contain a 14-carbon ring. These diterpenoids interact with AChRs in complex ways: as irreversible inhibitors at the agonist sites, as noncompetitive inhibitors, or as positive modulators, but no cembranoid was ever shown to have agonistic activity on AChRs. The cembranoid eupalmerin acetate displays positive modulation of agonist-induced currents in the muscle-type AChR and in the related gamma-aminobutyric acid (GABA) type A receptor. Moreover, cembranoids display important biological effects, many of them mediated by nicotinic receptors. Cembranoids from tobacco are neuroprotective through a nicotinic anti-apoptotic mechanism preventing excitotoxic neuronal death which in part could result from anti-inflammatory properties of cembranoids. Moreover, tobacco cembranoids also have anti-inflammatory properties which could enhance their neuroprotective properties. Cembranoids from tobacco affect nicotine-related behavior: they increase the transient initial ataxia caused by first nicotine injection into naive rats and inhibit the expression of locomotor sensitization to repeated injections of nicotine. In addition, cembranoids are known to act as antitumor compounds. In conclusion, cembranoids provide a promising source of lead drugs for many clinical areas, including neuroprotection, smoking-cessation, and anti-cancer therapies.

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Section: Mechanisms Of Cembranoid Actions On Nicotinic Receptorsmentioning

confidence: 99%

Actions of octocoral and tobacco cembranoids on nicotinic receptors

Ferchmin

Pagán

Ulrich

et al. 2009

Toxicon

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“…Our group discovered that certain cembranoids are noncompetitive inhibitors of nicotinic acetylcholine receptors (nAChRs) (Eterovic et al, 1993; Ferchmin et al, 2001; Hann et al, 1998). As one of cembranoids, 4R (Fig.…”

Section: Introductionmentioning

confidence: 99%

Neuroprotective activity of (1S,2E,4R,6R,-7E,11E)-2,7,11-cembratriene-4,6-diol (4R) in vitro and in vivo in rodent models of brain ischemia

Martins

et al. 2015

Neuroscience

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(1S,2E,4R,6R,-7E,11E)-2,7,11-cembratriene-4,6-diol (4R) is a precursor to key flavor ingredients in leaves of Nicotiana species. The present study shows 4R decreased brain damage in rodent ischemic stroke models. The 4R-pretreated mice had lower infarct volume (26.2±9.7 mm3) than those in control groups (untreated: 63.4±4.2 mm3, DMSO: 60.2±14.2 mm3). The 4R-posttreated rats also had less infarct volume (120±65 mm3) than those in the rats of DMSO group (291±95 mm3). The results from in vitro experiments indicate that 4R decreased neuro2a cells (neuroblastoma cells) apoptosis induced by oxygen glucose deprivation (OGD), and improved the population spikes (PSs) recovery in rat acute hippocampal slices under OGD; a phosphatidylinositol 3-kinase (PI3K) inhibitor, wortmannin, abolished the effect of 4R on PSs recovery. Furthermore, 4R also inhibited monocyte adhesion to bEND5 cells (murine brain-derived endothelial cells) and upregulation of intercellular adhesion molecule-1(ICAM-1) induced by OGD/reoxygenation (OGD/R), and restored the p-Akt level to pre-OGD/R values in bEND5 cells. In conclusion, the present study indicates that 4R has a protective effect in rodent ischemic stroke models. Inhibition of ICAM-1 expression and restoration of Akt phosphorylation are the possible mechanisms involved in cellular protection by 4R.

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“…Diverse and often novel lipid metabolites have been identified in cnidarians including prostaglandins (Koljak et al, 2001), steroids and sterols (Fleury et al, 2008;Qi et al, 2008), and other terpenoids (Eterovic et al, 1993;Frenz-Ross et al, 2008). Many of these compounds have been discovered through prospecting for natural products with biomedical applications, particularly in soft-bodied anthozoans (e.g., zoanthids, gorgonians and alycyonaceans).…”

Section: Steroid Metabolism In Cnidariansmentioning

confidence: 99%

Steroid metabolism in cnidarians: Insights from Nematostella vectensis

Tarrant

Reitzel

Blomquist

et al. 2009

Molecular and Cellular Endocrinology

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Cnidarians occupy a key evolutionary position as a sister group to bilaterian animals. While cnidarians contain a diverse complement of steroids, sterols, and other lipid metabolites, relatively little is known of the endogenous steroid metabolism or function in cnidarian tissues. Incubations of cnidarian tissues with steroid substrates have indicated the presence of steroid metabolizing enzymes, particularly enzymes with 17β-hydroxysteroid dehydrogenase (17β-HSD) activity. Through analysis of the genome of the starlet sea anemone, Nematostella vectensis, we identified a suite of genes in the short chain dehydrogenase/reductase (SDR) superfamily including homologs of genes that metabolize steroids in other animals. A more detailed analysis of Hsd17b4 revealed complex evolutionary relationships, apparent intron loss in several taxa, and predominantly adult expression in N. vectensis. Due to its ease of culture and available molecular tools N. vectensis is an excellent model for investigation of cnidarian steroid metabolism and gene function. KeywordsEvolution, hydroxysteroid dehydrogenase, short chain dehydrogenase/reductase Abbreviations CYP HSD AKR 3

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Diterpenoids from caribbean gorgonians act as noncompetitive inhibitors of the nicotinic acetylcholine receptor

Cited by 21 publications

References 16 publications

Actions of octocoral and tobacco cembranoids on nicotinic receptors

Actions of octocoral and tobacco cembranoids on nicotinic receptors

Neuroprotective activity of (1S,2E,4R,6R,-7E,11E)-2,7,11-cembratriene-4,6-diol (4R) in vitro and in vivo in rodent models of brain ischemia

Steroid metabolism in cnidarians: Insights from Nematostella vectensis

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