Cholinergic receptors activators

The clinical application of alkaloids involves them as agents to regulate mescaric cholinergic receptor activity and repairing possible disturbances or to correct possible defects. Atropine, hyoscine and hyoscyamine may all have these kinds of applications. 

Inhibition of AChE leads to a net accumulation of synaptic ACh levels, with persistent activation of cholinergic receptors on poslsynaptic cells. Under normal conditions, this shift to enhanced cholinergic receptor activation leads to functional signs and symptoms of cholinergic... 

Nicotinic Receptor Agonists. There has been significant activity in the development of muscarinic cholinergic receptor agonists for dementia. In addition, agents that interact with nicotinic cholinergic receptors may also have therapeutic value. Nicotinic receptors have been reported to be... 

Low concentrations of solubilised jS-albumin inhibit ACh release in slices from rat hippocampus and cortex areas which show degeneration in AzD, but not in slices from the striatum which is unaffected. While not totally specific to ACh, since some inhibition of NA and DA and potentiation of glutamate release have been reported, this effect is achieved at concentrations of A/i below those generally neurotoxic. Since jS-amyloid can inhibit choline uptake it is also possible (see Auld, Kar and Quiron 1998) that in order to obtain sufficient choline for ACh synthesis and the continued function of cholinergic neurons, a breakdown of membrane phosphatidyl choline is required leading to cell death (so-called autocannibalism), /i-amyloid can also reduce the secondary effects of Mi receptor activation such as GTPase activity... 

Gronier, B. Rasmussen, K. (1998). Activation of midbrain presumed dopaminergic neurones by muscarinic cholinergic receptors an in vivo electrophysiological study in the rat. Br. J. Pharmacol. 124, 455-64. 

ACh regulates the cortical arousal characteristic of both REM sleep and wakefulness (Semba, 1991, 2000 Sarter Bruno, 1997, 2000). Medial regions of the pontine reticular formation (Figs. 5.2 and 5.7) contribute to regulating both the state of REM sleep and the trait of EEG activation. Within the medial pontine reticular formation, presynaptic cholinergic terminals (Fig. 5.1) that release ACh also are endowed with muscarinic cholinergic receptors (Roth et al, 1996). Autoreceptors are defined as presynaptic receptors that bind the neurotransmitter that is released from the presynaptic terminal (Kalsner, 1990). Autoreceptors provide feedback modulation of transmitter release. Autoreceptor activation... 

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). 

Activation of 5-HT2A and 5-HT2c receptors enhances the release of ACh in the mPFC and the hippocampus, and of DA in the mPFC and the VTA of the rat. Thus, the increased availability of DA and ACh at central sites after 5-HT2A/2C receptor activation could be responsible, at least in part, for the increased incidence of W. Mesopontine cholinergic cells do not express 5-HT2A/2C receptors. The LDT/PPT... 

Muscle-relaxant A drug that relaxes skeletal (voluntary) muscle either directly by blocking nicotinic cholinergic receptors or indirectly through the activation of inhibitory spinal cord interneurons. 

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). 

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