Naslov
Evaluation of Δ9-tetrahydrocannabinol potency to inhibit cholinesterases

Autori
Žunec, Suzana ; Katalinić, Maja

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, ostalo

Izvornik
Book of Abstracts of the Congress of the Croatian Society of Biochemistry and Molecular Biology ˝Crossroads in Life Sciences˝, HDBMB2019 / Katalinić, Maja ; Dulić, Morana ; Stuparević, Igor - Zagreb, 2019, 137-137

Skup
Congress of the Croatian Society of Biochemistry and Molecular Biology "Crossroads in Life Sciences" (HDBMB2019)

Mjesto i datum
Lovran, Hrvatska, 25.09.2019. - 28.09.2019

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
THC, acetylcholinesterase, butyrylcholinestarse

Sažetak
The Cannabis sativa L. main psychotropic constituent, cannabinoid Δ9- tetrahydrocannabinol (THC), has been widely explored for its antiemetic, anticonvulsive, antiinflammatory, and analgesic properties. These effects are attributed to THC binding to the family of cannabinoid receptors found primarily on central and peripheral neurons (CB1) or immune cells (CB2). However, the existing knowledge on THC is controversial in many aspects. It is known that acute THC effects are related to disturbed functioning in performance and cognitive tasks (reaction time, motor coordination and attention, learning perception). It has been shown also that THC reduced the synthesis of the neurotransmitter acetylcholine in the hippocampus pointing to its negative effects on cognitive processes. On the other hand, based on a high lipophilicity and a fused tricyclic structure of THC, some authors hypothesized that it could bind to acetylcholinesterase (AChE, EC 3.1.1.7). Inhibition of this enzyme by THC may result with an improvement of neurological deficits. Namely, computational modelling of the THC-AChE interactions demonstrated that THC could bind to the allosteric peripheral anionic site (PAS) of AChE which is linked to the etiology of Alzheimer's disease as a concomitant prevention of AChE-promoted Aß aggregation. Further on, the other homologous enzyme butyrylcholinesterase (BChE, EC 3.1.1.8) which is present in neuritic plaques together with AChE, could also be a target for THC inhibition, due to the similar active site In this study we tested the ability of THC to inhibit human AChE and BChE. As results indicate, THC inhibited both enzymes in the micromolar range with certain selectivity for BChE. Obtained plots suggest a competitive mode of THC action for both enzymes. Obtained results confirm that beside activity at endocannabinoid system, THC also affects other neuronal systems, including central cholinergic neurotransmission crucial for cognitive functions.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

POVEZANOST RADA