Nicotinic acetylcholine receptor subunit ACR-16 (ACR-16) (ACR-16)

The Nicotinic acetylcholine receptor subunit ACR-16 is a critical component of the cholinergic signaling system in various nematode species, including the model organism Caenorhabditis elegans and significant human and animal parasites like Ascaris suum and hookworms [1, 3, 5]. It typically assembles into homopentameric, nicotine-sensitive ion channels, often referred to as N-type receptors, which are pharmacologically distinct from the levamisole-sensitive L-type receptors [4, 6]. These receptors are widely distributed in parasite tissues, including body wall muscles, where they mediate excitatory neurotransmission and are essential for normal locomotion [3, 11]. ACR-16 is a high-priority target for anthelmintic development because its unique pharmacological profile allows for the potential discovery of selective agents that do not affect host receptors [1, 2]. Drugs targeting ACR-16, such as nicotine-like agonists or negative allosteric modulators, aim to disrupt the parasite's neuromuscular control, leading to paralysis and eventual expulsion from the host [1, 9]. However, the high degree of sequence conservation between nematode ACR-16 and the vertebrate alpha7 nicotinic receptor presents a significant challenge for achieving the necessary therapeutic selectivity [3, 13]. Research into this target is driven by the urgent need for new anthelmintics to overcome widespread resistance to existing drugs like levamisole and pyrantel [2, 7]. Functional expression of ACR-16 in systems like Xenopus oocytes has enabled the screening of novel compounds, including plant-derived monoterpenes and synthetic allosteric modulators [9, 10]. Understanding the specific subunit composition and accessory protein requirements, such as RIC-3, is vital for accurately modeling the receptor's behavior in vivo [6, 12]. Overall, ACR-16 represents a promising yet complex target for the next generation of antiparasitic therapies [1, 5].

Other names

Parasitic nicotinic acetylcholine receptor ACR-16Asu-ACR-16Aca-ACR-16Nam-ACR-16Ace-ACR-16alpha7-like nicotinic acetylcholine receptorN-type nicotinic acetylcholine receptorN-AChR

Agonists bind to the orthosteric site of the homomeric receptor, causing the ion channel to open and allow cation influx, which leads to membrane depolarization and spastic paralysis of the parasite; antagonists and negative allosteric modulators block this activity to disrupt locomotion.