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• W2317758470 abstract "The dietary oxylipins falcarinol (1a) and falcarindiol (1b) trap thiols by direct nucleophilic addition to their diyne system, but despite this, only falcarinol (1a) is a reversible agonist of cannabinoid receptors, providing a rationale for comparing their activity also on other neuronal targets. Because GABAA receptors (GABAARs) are exquisitely sensitive to polyacetylenic oxylipins in terms of either potentiation (falcarindiol, 1b) or inhibition (oenanthotoxin, 2a), the activity of 1a was investigated on synaptic (α1β2γ2L) and extrasynaptic (α1β2δ and α1β2) subtypes of GABAARs. Falcarinol (1a) significantly enhanced the amplitude of currents mediated by α1β2γ2L receptors, but this effect was associated with a use-dependent block. Conversely, α1β2 receptors were inhibited without any sign of use-dependent block for the entire range of concentrations tested (1–10 μM). Interestingly, responses mediated by α1β2δ receptors, showing no or very little macroscopic desensitization, were strongly potentiated by 1a, exhibiting a fading reminiscent of macroscopic desensitization. When compared to the activity of falcarindiol (1b), falcarinol (1a) showed a higher affinity for GABAARs and, overall, a substantially different profile of pharmacological action. Taken together, the present data support the view that modulation of GABAARs might underlie the insecticidal and sedative activity of falcarinol (1a)." @default.
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• W2317758470 date "2014-12-04" @default.
• W2317758470 modified "2023-10-14" @default.
• W2317758470 title "Dietary Acetylenic Oxylipin Falcarinol Differentially Modulates GABA_A Receptors" @default.
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• W2317758470 doi "https://doi.org/10.1021/np500615j" @default.
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