Effect of OA689 on nicotinic acetylcholine receptors expressed on neurosecretory cells

master's thesis

• Title (english): Utjecaj OA689 na nikotinske acetilkolinske receptore eksprimirane na neurosekretornim stanicama
• Author: Ivona Čupić
• Mentor: Vladimir Mrša (mentor)
• Granter: University of Zagreb; Faculty of Food Technology and Biotechnology; (Department of Chemistry and Biochemistry); (Laboratory for Biochemistry); Zagreb
• Defense date and country: 2021-09-06, Croatia
• Scientific / art field, discipline and subdiscipline: BIOTECHNICAL SCIENCES; Biotechnology

Abstract

The aim of this study is to characterise the mode of action of the compound OA689 on dorsal unpaired median (DUM) neurons from the cockroach P. americana, using whole-cell patch-clamp technique. The compound OA689 is a ligand of nicotinic acetylcholine receptors (nAChRs) which are expressed in both vertebrate and invertebrate species. We demonstrated that OA689 does not act as a nAChR agonist, but rather as an antagonist or a negative allosteric modulator of nAChRs. The application of the compound at 8.29 μM reduces acetylcholine-induced current amplitudes by 50%. The inhibitory effect of OA689 was blocked in the presence of nicotinic acetylcholine receptor antagonists, α-bungarotoxin (α-Bgt) and methyllicaconitine (MLA), while the effect of OA689 was not blocked in the presence of mecamylamine (MEC). Our data support an action of OA689 through α-Bgt-sensitive homomeric α7 receptor. The same results were obtained when the effect of OA689 alone and in the presence of nAChR antagonists was examined on nicotine-induced currents suggesting that muscarinic receptors are not responsible for the inhibitory effect of OA689.

Abstract (croatian)

Cilj ovog istraživanja je okarakterizirati način djelovanja spoja OA689 na dorzalno neparnim medijalnim (eng. dorsal unpaired median, DUM) neuronima žohara P. americana, koristeći tehniku „whole-cell patch-clamp“. Spoj OA689 je ligand nikotinskih acetilkolinskih receptora (eng. nicotinic acetylcholine receptors, nAChRs) koji su eksprimirani i kod kralježnjaka i kod beskralježnjaka. Pokazano je da OA689 ne djeluje kao agonist nikotinskih acetilkolinskih receptora, već kao antagonist ili negativni alosterički modulator. Primjena spoja pri koncentraciji 8.29 μM smanjuje amplitude struje inducirane acetilkolinom za 50 %. Inhibitorni učinak OA689 je blokiran u prisutnosti antagonista nikotinskih acetilkolinskih receptora, α-bungarotoksina (α-Bgt) i metilikakonitina (MLA), dok učinak OA689 nije blokiran u prisutnosti mekamilamina (MEC). Rezultati dobiveni ovim istraživanjem podržavaju djelovanje OA689 putem α-Bgt-osjetljivog homomernog α7 receptora. Isti rezultati su postignuti kada je ispitivan učinak OA689 te učinak OA689 u prisutnosti antagonista nAChR na struje inducirane nikotinom, što ukazuje na to da muskarinski receptori nisu odgovorni za inhibitorni učinak OA689.

• Keywords: nicotinic receptor; insect; OA689; antagonist; negative allosteric modulator
• Keywords (english): nikotinski receptor; kukac; OA689; antagonist; negativni alosterički modulator
• Language: english
• URN:NBN: urn:nbn:hr:159:250573
• Study programme: Title: Molecular Biotechnology; Study programme type: university; Study level: graduate; Academic / professional title: magistar/magistra inženjer/inženjerka molekularne biotehnologije (magistar/magistra inženjer/inženjerka molekularne biotehnologije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Closed access
• Created on: 2022-05-26 11:33:49