Cholinergic receptors function

Elgoyhen, A., Vetter, D., Katz, E. etal. Alpha 10 a determinant of nicotinic cholinergic receptor function in mammalian vestibular and cochlear mechanosensory hair cells. Proc. Natl Acad. Sci. U.S.A. 98,3501-3506, 2001. 

Elgoyhen AB, Vetter DE, Katz E, RotWinCV, Heinemann SF, Boulter J (2001) alO a determinant of nicotinic cholinergic receptor function in mammalian vestibular and chochlear mechanosen-sory hair cells. Proc Natl Acad Sci 98 3501-3506 Fabian-Fine R, Skehel P, Erington ML, Davies HA, Sher E, Stewart MG, Fine A (2001) Ultra-structural distribution of the a7 nicotinic acetylcholine receptor subunit in rat hippocampus. J Neurosci 21 7993-8003... 

Paton WDM, Zaimis EJ (1949) The pharmacological actions of polymethylene bistrimethylammo-nium salts. Br J Pharmacol Chemother 4 381 00 Patrick J, Stallcup WB (1977) a-Bungarotoxin binding and cholinergic receptor function on a rat sympathetic nerve line. J Biol Chem 252 8629-8633 Patrick J, Boulter J, Deneris E, Wada K, Wada E, Connolly J, Swanson L, Heinemann S (1989) Structure and function of neuronal nicotinic acetylcholine receptors deduced from cDNA clones. Prog Brain Res 79 27-33... 

In contrast to all this negativity, it must be acknowledged that more is known about the structure and function of cholinergic receptors and synapses, especially the nicotinic ones, than for the receptors of any other NT. It is unfortunate that nicotinic synapses are not very common in the CNS. 

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). 

The intrinsic complexity and the multiplicity of cholinergic receptors became evident upon elucidation of their primary structures. In the CNS, at least nine different sequences of a subunits and three different sequences of (3 subunits of the nicotinic receptor have been identified [10, 11]. Expression of the cloned genes encoding certain subunit combinations yields functional receptors with different sensitivities toward various toxins and agonists. 

Abstract The discovery that mammalian brain expresses the mRNAs for nine different nicotinic cholinergic receptor subunits (a2-a7, p2-p4) that form functional receptors when expressed in Xenopus laevis oocytes suggests that many different types of nicotinic cholinergic receptors (nAChRs) might be expressed in the mammalian brain,. Using an historical approach, this chapter reviews some of the... 

Other mechanisms, such as the inhibition of -amyloid formation. There are several other alkaloids which are nicotinic agonists at the cholinergic receptor such as lobeline (89) from Lobelia inflata. Lobelia inflata a could be exploited to influence cholinergic function in AD. Sophoramine (90) and cytisine (91), found in members of the Leguminosae, have nicotinic actions but they do not appear to have been developed for any pharmaceutical purposes, probably because of their toxicity. 

B. M. Conti-Tronconi, M. A. Raftery (1982). The nicotinic cholinergic receptor correlations of molecular structure with functional properties. Annu. Rev. Biochem. 5P. 491-530. 

Stimulation of postsvnaptic cholinergic receptors with so-called cholino-mimetics, i.e. compounds that can mimic some functions of acetylcholine at cholinergic synapses. This approach, which included experimental compounds such as RS 86 (Wettstein and Spiegel, 1984), xanomeline (Sramek et t//., 1995) and AF 102B (Fischer et t//., 1996), failed, possibly due to a lack of specificity of the molecules tested (Marin and Davis, 1998). 

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. 

Since there are two primary neurotransmitters involved in autonomic discharge, there are two primary classifications of postsynaptic receptors. Cholinergic receptors are located at acetylcholine synapses, and adrenergic receptors are located at norepinephrine synapses. As indicated in Figure 18-2, each type of receptor has several subclassifications. The location and functional significance of these classifications and subclassifications are presented here. 

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