Acetylcholine release muscarinic

Several cholinergic strategies, other than cholinesterase inhibition, have been employed with the intention of ameliora ting the symptoms of AD. These include precursor loading acetylcholine release enhancement, and direct activation of both muscarinic and nicotinic receptors. 

Roth, M. T., Fleegal, M. A., Lydic, R. Baghdoyan, H. A. (1996). Pontine acetylcholine release is regulated by muscarinic autoreceptors. Neuroreport 7, 3069-72. 

Douglas, C. L., Baghdoyan, H. A. Lydic, R. (2001). M2 muscarinic autoreceptors modulate acetylcholine release in prefrontal cortex of C57BL/6J mouse. 

Working-memory enhancement by nicotine is seen using delayed matching-to-sample tasks in monkeys (Terry et ai. 1993). This benefit is reversed by scopolamine, suggesting that nicotine s beneficiai effect is due to increased central acetylcholine release and subsequent actions at muscarinic receptors. Nicotine appears to shift female rats toward a male-typical navigational strategy, using spatial cues rather than landmarks (Kanit et al. 1998). 

Q24 blocks presynaptic muscarinic inhibition of acetylcholine release... 

The available data are consistent with the present thesis that cholinergic inputs to cerebral cortex mediate intradendritic events fundamental to conscious activity as a primary role, and that cholinergic modulation of electrophysiological activity may be secondary, even epiphenomenal. Transduction pathways exist whereby muscarinic receptors (and possibly nicotinic receptors acting presynaptically to inhibit acetylcholine release) may lead to actions on the cytoskeleton directly relevant to consciousness. The thesis presented here describes these pathways and also suggests a possible explanation for the diversity of neuromodulators and metabotropic receptors. Accordingly, qualitative aspects of our consciousness would be finely tuned by a number of neurochemicals, prominent among which is acetylcholine. 

Quera-Salva MA, Orluc A, Goldenberg F, et al Insomnia and use of hypnotics study of a French population. Sleep 14(5) 386-391, 1991 Quirion R, Richard J, Wilson A Muscarinic and nicotinic modulation of cortical acetylcholine release monitored by in vivo microdialysis in freely moving rats. Synapse 17 92-100, 1994... 

Stimulation of the parasympathetic nervous system modifies the organ functions by two main pathways. Firstly, the acetylcholine released from parasympathetic nerves can activate muscarinic receptors which are present in gland cells (sweat glands), smooth muscles and heart. The... 

Effects of increasing doses of atropine on heart rate (A) and salivary flow (B) compared with muscarinic receptor occupancy in humans. The parasympathomimetic effect of low-dose atropine is attributed to blockade of prejunctional muscarinic receptors that suppress acetylcholine release. 

Activation of endothelial cell muscarinic receptors by acetylcholine releases endothelium-derived relaxing factor (nitric oxide) (EDRF [NO]), which causes relaxation of vascular smooth muscle precontracted with norepinephrine. Removal of the endothelium by rubbing eliminates the relaxant effect and reveals contraction caused by direct action of acetylcholine on vascular smooth muscle. (Modified and reproduced, with permission, from Furchgott RF, Zawadzki JV The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature 1980 288 373.)... 

Effects of increasing doses of atropine on heart rate (A) and salivary flow (B) compared with muscarinic receptor occupancy in humans. The parasympathomimetic effect of low-dose atropine is attributed to blockade of prejunctional muscarinic receptors that suppress acetylcholine release. (Modified and reproduced, with permission, from Wellstein A, Pitschner HF Complex dose-response curves of atropine in man explained by different functions of Mi and M2 cholinoceptors. Naunyn Schmiedebergs Arch Pharmacol 1988 338 19.)... 

Slutsky I, Wess J, Gomeza J, Dudel J, Pamas I, Parnas H (2003) Use of knockout mice reveals involvement of M2-muscarinic receptors in control of the kinetics of acetylcholine release. J Neurophysiol 89 1954-67... 

In the peripheral (Wessler 1989) as well as central (Wonnacott 1997) nervous system, presynaptic nicotinic autoreceptors were reported to control the release of acetylcholine. In both locations, the consequence of presynaptic nAChR activation most commonly is an increase in both spontaneous and evoked acetylcholine release (MacDermott et al. 1999), whereas presynaptic muscarinic receptors mediate the opposite effect, an autoinhibition. Recent studies have focused on the composition of presynaptic nAChRs (Table 2). In the hippocampus, nicotinic autoreceptors were suggested to be a3/p4 receptors (Tani et al. 1998), but a role of p2 subunits has also been implicated (Lloyd et al. 1998). Likewise, in the neocortex, presynaptic nicotinic autoreceptors are likely to be 04/ p2 receptors (Marchi et al. 2002). In contrast, in the interpeduncular nucleus the autoreceptors were suggested to mainly contain a3 and p4 subunits (Grady et al. 2001). 

Cassel JC, Jeltsch H, Neufang B, Lauth D, Szabo B, Jackisch R. Downregulation of muscarinic- and 5-HT IB-mediated modulation of [3H]acetylcholine release in hippocampal slices of rats with fimbria-fornix lesions and intrahippocampal grafts of septal origin. Brain Res 1995 704 153-166. 

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