Muscarinic cholinergic subtypes

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). 

Costa, P., Traver, D.J., Auger, C.B. and Costa, L.G. (1994) Expression of cholinergic muscarinic receptor subtypes mRNA in rat blood mononuclear cells. Immuno-pharmacology 28,113—123. 

Thus, cholinergic receptor classification can be considered in terms of three stages of development. Initially, Dale [2] distinguished nicotinic and muscarinic receptor subtypes with crude alkaloids. Then, chemical synthesis and structure-activity relationships clearly revealed that nicotinic and muscarinic receptors were heterogeneous, but chemical selectivity could not come close to uncovering the true diversity of receptor subtypes. Lastly, analysis of subtypes came from molecular cloning, making possible the classification of receptors on the basis of primary structure (Fig. 11-2). 

Cortes R, Palacios JM. (1986). Muscarinic cholinergic receptor subtypes in the rat brain. I. 

Vilaro MT, Palacios JM, Mengod G. 1994. Multiplicity of muscarinic autoreceptor subtypes Comparison of the distribution of cholinergic cells and cells containing mRNA for five subtypes of muscarinic receptors in the rat brain. Mol Brain Res 21 30-46. 

Salamone, J. D., Correa, M., Carlson, B. B., Wisniecki, A., Mayorga, A. J., Nisenbaum, E., Nisenbaum, L., Felder, C. Neostriatal muscarinic receptor subtypes involved in the generation of tremulous jaw movements in rodents. Implications for cholinergic involvement in Parkinsonism, Life Sci. 2001, 68, 2579-2584. 

FIGURE 12—10. Acetylcholine (ACh) receptors. There are numerous receptors for ACh. The major subdivision is between nicotinic (N) and muscarinic (M) cholinergic receptors. There are also numerous subtypes of these receptors, best characterized for muscarinic receptor subtypes (Ml, M2, Mx). Perhaps the Ml postsynaptic receptor is key to mediating the memory functions linked to cholinergic neurotransmission, but a role for other cholinergic receptor subtypes has not been ruled out. 

Bymaster FP, Carter PA, Yamada M, Gomeza J, Wess J, Hamilton SE, Nathanson NM, McKinzie DL, Felder CC (2003a) Role of specific muscarinic receptor subtypes in cholinergic parasympathomimetic responses, in vivo phosphoinositide hydrolysis, and pilocarpine-induced seizure activity. The Eur J Neurosci 17 1403-10... 

Eglen RM (2006) Muscarinic receptor subtypes in neuronal and non-neuronal cholinergic function. Auton Autacoid Pharmacol 26 219-33... 

Wolfe BB, Yasuda RP (1995) Development of selective antisera for muscarinic cholinergic receptor subtypes. Ann NY Acad Sci 757 186-93... 

Cholinergic receptors in iris sphincter tissue and ciliary body have been shown to be of the muscarinic type. Five muscarinic receptor subtypes (M1-M5) have been identified. Sixty percent to 75% of the muscarinic receptors in the human iris sphincter and ciliary body are M3, and 5% to 10% are M2 and M4. Approximately 7% of receptors in the ciliary processes and iris sphincter are of the Ml subtype. Approximately 5% of receptors present in the iris sphincter are M5. Inhibition of these receptors by cholinergic antagonists induces pupillary dilation (mydriasis) and paralysis of accommodation (cycloplegia) and may elevate intraocular pressure (lOP), particularly in patients with predisposing risk factors. 

Watson, M. et ah, 1986. pH]Pirenzepine and (-)-[ H]quinuclidinyl benzilate binding to rat cerebral cortical and cardiac muscarinic cholinergic sites I. Characterization and regulation of agonist binding to putative muscarinic subtypes. J. Pharmacol. Exp. Ther. 237, 411-418. 

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