Modulation of ACh release

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). 

Graves AR, Lewin KA, Lindgren C. 2004. Nitric oxide, cAMP and the biphasic muscarinic modulation of ACh release at the lizard neuromuscular junction. J Physiol 559 423-432. 

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... 

The concentrations of Tat able to activate mGluRl and modulate directly ACh release (Feligioni et al. 2003) or, through interactions with NMDA receptors, NA release (Longordo et al. 2006) are lower than those reported to cause overt neurotoxicity (Nath and Geiger 1998). It is therefore possible that mGluRl represents a... 

Earlier studies with /-tubocurarine and atropine indicated that nicotinic and muscarinic ACh receptor blockers can modulate the release of ACh induced by an inhibitor of AChE (Carlson and Dettbam, 1987, 1988). The effects of these dmgs, whether inhibiting or stimulating ACh release, are concentration dependent and determined by the frequency of nerve activity (Bowman, 1980 Wessler et al, 1987a, b). Therefore, dmgs that reduce axonal hyperexcitability by decreasing amount of ACh released from the nerve terminals without interfering with normal transmission... 

Fig. 11.4. Model for cholinergic signalling in the intestinal mucosa, providing a possible rationale for AChE secretion by parasitic nematodes. ACh released from enteric cholinergic motor neurons stimulates chloride secretion, mucus secretion and Paneth cell exocytosis through muscarinic receptors. Secretory responses may be modulated by mast cell mediators, either directly or via the induction of neural reflex programmes. The role of muscarinic receptor-positive cells in the lamina propria of rats infected with N. brasiliensis is undetermined, as are potential mechanisms of trans-epithelial transport of the enzymes. Adapted from Cooke (1984).

Acetylcholine release. Policosanol produced some interactions in the modulation of the acetylcholine (ACh) release at the mouse neuromuscular junction. Policosanol enhanced to a small extent either the spontaneous or the evoked ACh release. An increase in the rate of the conformational change induced at the nicotinic receptor-channel complex by ACh was also observed L... 

Tacrine has been found to be somewhat effective in patients with mild-to-moderate symptoms of this disease for improvement of cognitive functions. The drug is primarily a reversible cholinesterase inhibitor that increases the concentration of functional ACh in the brain. However, the pharmacology of tacrine is complex the drug also acts as a muscarinic receptor modulator in that it has partial agonistic activity, as well as weak antagonistic activity on muscarinic receptors in the CNS. In addition, tacrine appears to enhance the release of ACh from cholinergic nerves, and it may alter the concentrations of other neurotransmitters such as dopamine and NE. 

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