Muscarinic receptors function

Birdsall NJ, Farries T, Gharagozloo P, Kobayashi S, Lazareno S, Sugimoto M. Subtype-selective positive cooperative interactions between brucine analogs and acetylcholine at muscarinic receptors functional studies. Mol Pharmacol 1999 55 778-786. 

Jacobson, K.A. et al. (1995) Molecular probes for muscarinic receptors Functionalized congeners of selective muscarinic antagonists. Life Sci. 56(11/12), 823-830. 

Stengel, R W., Gomeza, J., Wess, J. and Cohen, M. L. M2 and M4 receptor knockout mice muscarinic receptor function in cardiac and smooth muscle in vitro. /. Pharmacol. Exp. Ther. 292 877-85, 2000. 

Tandon P, Padilla S, Barone S Jr, et al Fenthion produces a persistent decrease in muscarinic receptor function in the adult rat retina. Toxicol Appl Pharmacol 125 271-280, 1994... 

Lein, P.J., Fryer, A.D. (2005). Organophosphorus insecticides induce airway hyperreactivity by decreasing neuronal M2 muscarinic receptor function independent of acetylcholinesterase inhibition. Toxicol. Sci. 83 166-76. 

Muscarinic receptors are glycoproteins with molecular weights of approximately 80,000. They are located on the outer surface of the cell membrane, and they are of the G-protein-linked type M, Mg, and Mg receptors couple with proteins to stimulate phospho-lipase-C, whereas Mg and M4 receptors couple with Gi proteins to inhibit adenylate cyclase (25). The molecular basis of muscarinic receptor function has been reviewed (26). Nordvall and Hacksell (27) proposed a molecular model of the transmembrane domains of the receptor, to explain the three-dimensional interaction of the receptor with its ligands. However, the authors specified that the model is "primarily of qualitative value". 

Gambune, L. M.. Ellxm, C. L., and Fryer. A. D. (1994). Ozonc-induced loss of neuronal. M2 muscarinic receptor function is prevented by cyclophosphamide. /. Appl Physiol 77, 1492-1499. 

Soukup, O., Kumar, U.K., Proska, J., et al., 2011. The effect of oxime reactivators on muscarinic receptors. Functional and binding examinations. Envir. 

The mink Mustela vision) is a piscivorous mammal that also has been exposed to relatively high dietary levels of methyl mercury in North America in recent times. In a Canadian study, mink trapped in Yukon territory, Ontario, and Nova Scotia were analyzed for levels of mercury and abundance of muscarinic, cholinergic and dopaminergic receptors in the brain (Basu et al. 2005). A correlation was found between total Hg levels and abundance of muscarinic receptors, but a negative correlation was found between total Hg and abundance of dopaminergic receptors. Thus, it was suggested that environmentally relevant concentrations of Hg (much of it in methyl form) may alter neurochemical function. The highest levels of mercury contamination were found in mink from Nova Scotia that had a mean concentration of total Hg of 5.7 pg/g in brain, 90% of which was methyl mercury. 

Acetylcholinesterase is a component of the postsynaptic membrane of cholinergic synapses of the nervous system in both vertebrates and invertebrates. Its structure and function has been described in Chapter 10, Section 10.2.4. Its essential role in the postsynaptic membrane is hydrolysis of the neurotransmitter acetylcholine in order to terminate the stimulation of nicotinic and muscarinic receptors (Figure 16.2). Thus, inhibitors of the enzyme cause a buildup of acetylcholine in the synaptic cleft and consequent overstimulation of the receptors, leading to depolarization of the postsynaptic membrane and synaptic block. 

Figure 6.4 Schematic representation of the muscarinic receptor. All muscarinic receptors have seven transmembrane domains and the major difference between them is within the long cytoplasmic linkage connecting the fifth and sixth domains. This implies different G-protein connections and functions. Some possibilities are shown although the position of the Mi and M2 boxes is not intended to indicate their precise structural differences within the loop...

EEG slow waves. The differential EEG and ACh responses to dialysis delivery of AF-DX 116 (M2/M4) versus pirenzepine (M1/M4) supports the conclusion that, in B6 mouse, postsynaptic muscarinic receptors of the Ml subtype form one receptor mechanism by which ACh activates the EEG (Douglas et al, 2002a). The data summarized in Fig. 5.11 provide direct measures of G protein activation in basal forebrain and prefrontal cortex by muscarinic cholinergic receptors (DeMarco et al, 2004). The in vitro data of Fig. 5.11A indicate the presence of functional muscarinic receptors in regions of B6 mouse prefrontal cortex where in vivo microdialysis studies (Douglas et al, 2002a, b) revealed modulation of ACh release and EEG by pre- and postsynaptic muscarinic receptors (Figs. 5.9 and 5.10). 

Caulfield, M. P. (1993). Muscarinic receptors - characterization, coupling and function. Pharmacol. Ther. 58, 319-79. 

ACh was first proposed as a mediator of cellular function by Hunt in 1907, and in 1914 Dale [2] pointed out that its action closely mimicked the response of parasympathetic nerve stimulation (see Ch. 10). Loewi, in 1921, provided clear evidence for ACh release by nerve stimulation. Separate receptors that explained the variety of actions of ACh became apparent in Dale s early experiments [2]. The nicotinic ACh receptor was the first transmitter receptor to be purified and to have its primary structure determined [3, 4]. The primary structures of most subtypes of both nicotinic and muscarinic receptors, the cholinesterases (ChE), choline acetyltransferase (ChAT), the choline and ACh transporters have been ascertained. Three-dimensional structures for several of these proteins or surrogates within the same protein family are also known. 

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