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Papers of the Week

Papers: 30 Dec 2023 - 5 Jan 2024


Front Pharmacol



Inhibition of nicotinic acetylcholine receptors by oligoarginine peptides and polyamine-related compounds.


Ojomoko LO, Kryukova EV, Egorova NS, Salikhov AI, Epifanova LA, Denisova DA, Khomutov AR, Sukhov DA, Vassilevski AA, Khomutov MA, Tsetlin VI, Shelukhina IV


Oligoarginine peptides, known mostly for their cell-penetrating properties, are also inhibitors of the nicotinic acetylcholine receptors (nAChRs). Since octa-arginine (R8) inhibits α9α10 nAChR and suppresses neuropathic pain, we checked if other polycationic compounds containing amino and/or guanidino groups could be effective and tested the activity of the disulfide-fixed “cyclo”R8, a series of biogenic polyamines (putrescine, spermidine, and spermine), -methylated spermine analogs, agmatine and its analogs, as well as acylpolyamine argiotoxin-636 from spider venom. Their inhibitory potency on muscle-type, α7 and α9α10 nAChRs was determined using radioligand analysis, electrophysiology, and calcium imaging. “Cyclo”R8 showed similar activity to that of R8 against α9α10 nAChR (IC ≈ 60 nM). Biogenic polyamines as well as agmatine and its analogs displayed low activity on muscle-type , as well as α7 and α9α10 nAChRs, which increased with chain length, the most active being spermine and its -methylated derivatives having IC of about 30 μM against muscle-type nAChR. Argiotoxin-636, which contains a polyamine backbone and terminal guanidino group, also weakly inhibited nAChR (IC ≈ 15 μM), but it revealed high potency against rat α9α10 nAChR (IC ≈ 200 nM). We conclude that oligoarginines and similar polycationic compounds effectively inhibiting α9α10 nAChR may serve as a basis for the development of analgesics to reduce neuropathic pain.