European Journal of Pharmacology: Molecular Pharmacology
Potentiation and inhibition of subtypes of neuronal nicotinic acetylcholine receptors by Pb2+
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2020, TrAC - Trends in Analytical ChemistryCitation Excerpt :Pb2+ can depress the calcium current evoked by ryanodine receptor activation and possibly increase the concentration of intracellular Ca2+, impairing the long-term potentiation of hippocampal neurons [82,83]. Pb2+ is also able to affect the postsynaptic response in neurotransmission by binding with certain subunits of nAChR [84]. Mercury is able to degenerate the nervous system and disturb neuronal excitability.
Positive allosteric modulators as an approach to nicotinic acetylcholine receptor-targeted therapeutics: Advantages and limitations
2011, Biochemical PharmacologyCitation Excerpt :With site-directed cysteine mutations and reactive sulfhydryl reagents, residues E59 and H162 on the α4 subunit were found to be critical for potentiation by zinc, potentially forming part of the zinc binding site at subunit interfaces not containing the orthosteric site [34]. Potentiating effects of lead ions were observed on α3β2 receptors at concentrations between 1 and 250 μM, while similar concentrations inhibited responses by α3β4 and α4β2 receptors [35]. Naturally synthesized steroids (i.e. progesterone, testosterone, estradiol, corticosterone) were shown to exert allosteric effects on heteromeric α4-containing and α3-containing nAChR, the effects however, are generally inhibitory at low μM concentrations [36–39].
Presynaptic malfunction: The neurotoxic effects of cadmium and lead on the proton gradient of synaptic vesicles and glutamate transport
2011, Neurochemistry InternationalCitation Excerpt :Lead alters synaptic transmission by disrupting activity of Ca2+-regulated proteins, including protein kinases, voltage-gated Ca2+ channels, and Ca2+-binding proteins that control mobilization and docking of synaptic vesicles (Atchison, 2003; Braga et al., 1999a, b; Suszkiw, 2004). Ionotropic receptors, such as N-methyl-D-aspartate receptors and α7∗ nAChRs (Pereira et al. 2002; Vizi and Kiss 1998), are sensitive to micromolar concentrations of Pb2+ (Braga et al., 2004; Guilarte and Miceli, 1992; Marchioro et al., 1996; Mike et al., 2000; Si and Lee, 2003; Ujihara and Albuquerque, 1992; Ishihara et al., 1995; Zwart et al., 1995). The symptoms of acute lead poisoning are headache, irritability, and abdominal pain.
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