Inter- and Intracellular Signaling in Plant Cells with Participation of Neurotransmitters (Biomediators)
Akula Ramakrishna, Victoria V. Roshchina in Neurotransmitters in Plants, 2018
Contractile effects of acetylcholine connected with membrane ion permeability were also observed in the regulation of the stomata function—the opening and closing movement in plants such as V. faba and P. sativum (Wang et al. 1998, 1999a, 2000). It was established that muscarinic and nicotinic acetylcholine receptors are involved in the event. A regulatory role for acetylcholine and its antagonists in inward rectified K+ channels from guard cells protoplasts from leaf stomata of V. faba was found (Leng et al. 2000). Ca2+ and Ca-related systems were found to participate in acetylcholine-regulated signal transduction during stomata opening and closing (Wang et al. 2003a; Meng et al. 2004). Smolinski and Gorska-Brylass (1994) have also shown cholinesterase activity in stomata of Marchantia.
Stimulants and psychedelics
Ilana B. Crome, Richard Williams, Roger Bloor, Xenofon Sgouros in Substance Misuse and Young People, 2019
Nicotine is a potent parasympathomimetic alkaloid found in the Solanaceae (‘nightshade’) family of plants such as the tobacco plant (nicotiana tabacum) (Mohlenbrock, 1990). Nicotine is primarily a nicotinic acetylcholine receptor (nAChR) agonist, but acts as an antagonist in the nAChRa9 and nAChrRa10 receptors (Lester et al., 2009; Dani, 2015). It has been postulated that ‘it is unique in comparison to most drugs, as it generates normally incompatible physiological and psychological effects, namely increased arousal with decreased stress’ (Nesbitt, 1973), this is termed Nesbitt’s Paradox (Schachter, 1973). However, these changes are dependent upon various factors and, particularly, the degree of nicotine deprivation. Thus the relaxant properties of smoking reflect the relief of irritability, which develops between cigarettes (Parrott, 1998). Although, it has genuine stimulant properties, due to repeated abstinence effects, the average arousal level of smokers is generally similar to non-smokers. Nicotine constitutes approximately 0.6–3 per cent of the dry weight of tobacco and is present in the range of 2–7 μg/kg in various edible plants (Heiser and Heiser, 1987). It functions as an anti-herbivore chemical. Consequently, it was widely used as an insecticide in the past and some neo-nicotinoids are currently widely used (Arnason and Philogène, 1991). Nicotine is highly addictive and is the main contributor to the physiological dependence properties of tobacco smoking (D’Souza and Markou, 2011).
Functional characterisation of the GABAA receptors
Adam Doble, Ian L Martin, David Nutt in Calming the Brain: Benzodiazepines and related drugs from laboratory to clinic, 2020
The early photolabelling and peptide mapping experiments with the agonist muscimol suggested that it labelled the 13 subunits (Casalotti et al, 1986; Deng et al, 1986; Bureau and Olsen, 1988), although later studies suggested additional labelling of the a subunits (Smith and Olsen, 1994). Subsequent mutagenesis experiments have identified a number of residues in the N-terminal domain of both the α and β subunits that are important in channel activation. In the first of these experiments a single amino acid F64 of the al subunit when mutated to leucine (α1-F64L) produced a 200- fold decrease in the affinity of GABA and similar reductions in the affinity of the competitive antagonists bicuculline and SR 95531 (Sigel et al, 1992). More recent studies have demonstrated the importance of two neighbouring residues, R66 and S68, within this α subunit recognition loop, the evidence from which suggests that it is constrained within a β-strand (Boileau and Czajkowski, 1999). Four additional amino acids have been identified in the β subunits which appear to be important in agonist recognition: Y157, T160, T202 and Y205 (Amin and Weiss, 1993). By analogy with similar studies carried out on the nicotinic acetylcholine receptor, these amino acids have been allocated to loops B (Y157 and T160) and C (T202 and Y205) on the 13 subunits and loop D on the a subunit (F64). In each case it has been shown that mutagenesis in the homologous positions of the other subunits does not compromise channel activation, compatible with the notion that it is the αβ interface only which is important in the formation of the very low affinity (activating) site.
The α9α10 nicotinic acetylcholine receptor: a compelling drug target for hearing loss?
Published in Expert Opinion on Therapeutic Targets, 2022
Ana Belén Elgoyhen
Nicotinic acetylcholine receptors are a subfamily of the pentameric ligand-gated ion channels involved in many physiological and pathological processes [47]. Each receptor subtype is composed of different subunits, encoded by paralogous genes. They show a similar fivefold symmetrical arrangement of subunits around a central pore and are composed of extracellular and transmembrane (TM) domains (Figure 1). The extracellular domain contains the orthosteric ligand-binding sites and folds into a highly conserved immunoglobulin-like β-sandwich. The TM domain consists of four α-helices, with TM2 lining the channel pore, surrounded by a ring made of TM1 and TM3 α-helices [47,48]. According to their main tissue of expression, in vertebrates, they are divided into three subgroups: neuronal, muscle, and hair cell nAChRs [49]. Thus, neuronal nAChRs are formed by as yet not fully characterized combinatorial arrangements of α2-α7 (α8 in non-mammals) and β2-4 subunits [50–52]. In addition, receptors formed by the same subunits, but with alternate stoichiometry [53–58], further extend the complexity of neuronal nAChRs. On the other hand, muscle receptors are formed by α12 β1γ, and δ, or ε subunits [59,60]. Finally, and in contrast to neuronal receptors, the nAChR subunits expressed in cochlear hair cells have a very strict co-assembly pattern, encompassing only α9 and α10 subunits [61–63].
Mouse strain-specific acute respiratory effects of nicotine unrelated to nicotine metabolism
Published in Toxicology Mechanisms and Methods, 2019
A. J. Bloom
Nicotinic acetylcholine receptors expressed in the brainstem and spinal cord mediate central cholinergic regulation of respiration, including through their role in chemosensitivity, the ability of the nervous system to sense and respond to changing concentrations of CO2 in the blood. Acetylcholine and nicotine activate receptors in the preBötzinger complex, the site of normal respiratory rhythm generation in mammals, depolarizing inspiratory neurons, and increasing respiratory rate (Shao and Feldman 2009). Consistent with this, prior studies showed increased respiratory rate in most mouse strains tested one minute following intraperitoneal injection of nicotine at most concentrations (Marks et al. 1989). On the other hand, nicotine can also produce sedative effects in both humans and rodents (Acri 1994; Umezu 2012; Bernardi and Spanagel 2014).
The role of sugammadex, a novel cyclodextrin compound in modern anesthesia practice: conventional neuromuscular physiology and clinical pharmacology
Published in Expert Review of Clinical Pharmacology, 2019
Alan D. Kaye, Rachel J. Kaye, Elyse M. Cornett, Ivan Urits, Vwaire Orhurhu, Omar Viswanath, Amit Prabhakar
As a review of human physiology, the neuromuscular junction is comprised of several key components, including the presynaptic nerve terminal, synaptic cleft, and the post-synaptic nicotinic acetylcholine receptors on motor end-plates [2]. Action potentials propagated along the presynaptic neuron result in the release of acetylcholine into the synaptic cleft. These molecules then bind to two alpha subunits of the ionic post-junctional nicotinic acetylcholine receptors. Binding results in a conformational change in the ion channel prompting an influx of sodium and efflux of potassium. Dosing for neuromuscular blocker agents is typically based on an effective dose (ED) 95, which is the dose in which 95% twitch depression occurs in 50% of individuals [3]. For induction, one, two or three times the ED95 dose is typically administered and for maintenance dosing, the ED95 dosage is employed [3].