Neuronal Nicotinic Acetylcholine Receptors in Drosophila: Antibodies Against an ?-Like and a Non-?-Subunit Recognize the Same High-Affinity ?-Bungarotoxin Binding Complex

Neonicotinoid insecticides are used worldwide and have been demonstrated as toxic to beneficial insects such as honeybees. Their effectiveness is predominantly attributed to their high affinity for insect neuronal nicotinic acetylcholine receptors (nAChRs). Mammalian neuronal nAChRs are of major importance because cholinergic synaptic transmission plays a key role in rapid neurotransmission, learning and memory processes, and neurodegenerative diseases. Because of the low agonist effects of neonicotinoid insecticides on mammalian neuronal nAChRs, it has been suggested that they are relatively safe for mammals, including humans. However, several lines of evidence have demonstrated that neonicotinoid insecticides can modulate cholinergic functions through neuronal nAChRs. Major studies on the influence of neonicotinoid insecticides on cholinergic functions have been conducted using nicotine low-affinity homomeric α7 and high-affinity heteromeric α4β2 receptors, as they are the most abundant in the nervous system. It has been found that the neonicotinoids thiamethoxam and clothianidin can activate the release of dopamine in rat striatum. In some contexts, such as neurodegenerative diseases, they can disturb the neuronal distribution or induce oxidative stress, leading to neurotoxicity. This review highlights recent studies on the mode of action of neonicotinoid insecticides on mammalian neuronal nAChRs and cholinergic functions.

Download Full-text

The identification of novel structural compound classes exhibiting high affinity for neuronal nicotinic acetylcholine receptors and analgesic efficacy in preclinical models of pain

European Journal of Pharmacology ◽

10.1016/s0014-2999(00)00041-8 ◽

2000 ◽

Vol 393 (1-3) ◽

pp. 171-177 ◽

Cited By ~ 29

Author(s):

Michael D. Meyer ◽

Michael W. Decker ◽

Lynne E. Rueter ◽

David J. Anderson ◽

Michael J. Dart ◽

...

Keyword(s):

Nicotinic Acetylcholine Receptors ◽

Acetylcholine Receptors ◽

Analgesic Efficacy ◽

Neuronal Nicotinic Acetylcholine Receptors ◽

Preclinical Models ◽

Nicotinic Acetylcholine ◽

High Affinity

Download Full-text

Novel Three-Finger Neurotoxins from Naja melanoleuca Cobra Venom Interact with GABAA and Nicotinic Acetylcholine Receptors

Toxins ◽

10.3390/toxins13020164 ◽

2021 ◽

Vol 13 (2) ◽

pp. 164

Author(s):

Lina Son ◽

Elena Kryukova ◽

Rustam Ziganshin ◽

Tatyana Andreeva ◽

Denis Kudryavtsev ◽

...

Keyword(s):

Nicotinic Acetylcholine Receptors ◽

Gabaa Receptors ◽

Binding Sites ◽

Acetylcholine Receptors ◽

Nicotinic Acetylcholine ◽

High Affinity ◽

Central Loop ◽

Acetylcholine Binding Proteins ◽

Α7 Nachrs

Cobra venoms contain three-finger toxins (TFT) including α-neurotoxins efficiently binding nicotinic acetylcholine receptors (nAChRs). As shown recently, several TFTs block GABAA receptors (GABAARs) with different efficacy, an important role of the TFTs central loop in binding to these receptors being demonstrated. We supposed that the positive charge (Arg36) in this loop of α-cobratoxin may explain its high affinity to GABAAR and here studied α-neurotoxins from African cobra N. melanoleuca venom for their ability to interact with GABAARs and nAChRs. Three α-neurotoxins, close homologues of the known N. melanoleuca long neurotoxins 1 and 2, were isolated and sequenced. Their analysis on Torpedocalifornica and α7 nAChRs, as well as on acetylcholine binding proteins and on several subtypes of GABAARs, showed that all toxins interacted with the GABAAR much weaker than with the nAChR: one neurotoxin was almost as active as α-cobratoxin, while others manifested lower activity. The earlier hypothesis about the essential role of Arg36 as the determinant of high affinity to GABAAR was not confirmed, but the results obtained suggest that the toxin loop III may contribute to the efficient interaction of some long-chain neurotoxins with GABAAR. One of isolated toxins manifested different affinity to two binding sites on Torpedo nAChR.

Download Full-text