Cholinergic receptors postsynaptic

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). 

Acetylcholine. Most of the acetylcholine in the basal ganglia is found in the striatum, as the neurotransmitter of the large spiny interneurons, which account for about 3% of all striatal neurons. Both muscarinic and nicotinic cholinergic receptors are found in the striatum. Postsynaptic muscarinic receptors may inhibit transmitter release from... 

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. 

FIGURE 19-1 T Mechanism of action of cholinergic stimulants. Direct-acting stimulants bind directly to the postsynaptic cholinergic receptor. Indirect-acting stimulants inhibit the cholinesterase enzyme, thus allowing acetylcholine to remain in the synaptic cleft. 

Acetylcholine and agents acting at the autonomic ganglia or the neuromuscular junctions interact with nicotinic cholinergic receptors to initiate the end plate potential in muscle or an excitatory postsynaptical potential in nerve. The nicotinic receptor in skeletal muscle is a pentamer composed of four distinct subunits. 

Yamamura, H.L., Snyder. S H 1974 Postsynaptic localization of muscarinic cholinergic receptor binding in rat hippocampus. Brain Res. 78, 320-326. 

Figure 17-5 Hypothetical model of synthesis, storage, and release of ACh. (I) ACh is released from storage granules under the influence of the nerve action potential and Ca (2) ACh acts on postsynaptic cholinergic receptors. (3) Hydrolysis of ACh by AChE occurs in the synaptic cleft. (4) A high-affinity uptake system returns choline to the c osol. (5) ChAT synthesizes ACh in the cytosol, and the ACh is stored in granules (6) Glucose is converted to pyruvate, which is converted to acetyl-CoA in the mitochondria. Acetyl-CoA is released from the mitochondria by an acetyl carrier (7) Choline is also taken up into the neuron by a low-affinity uptake system and converted partly to phosphorylcholine.

Azinphos-methyl requires bioactivation for its action. The parent compound is activated to the potent oxon by microsomal mixed-function oxidase enzymes, which in turn elicits toxicity by inhibiting acetylcholinesterase in synapse and neuromuscular junctions. AChE inhibition leads to overstimulation of cholinergic receptors on postsynaptic neurons, muscle cells, and/or end-organs and consequent signs and symptoms of cholinergic toxicity. 

FIGURE 5.2 (See color insert following page 46.) Presynaptic and postsynaptic regions of the acetylcholine neuron, emphasizing the synthesis and degradation of acetylcholine and the cholinergic receptor suhtypes (Panel [A]) summary of the peripheral nervous system that utilizes acetylcholine as the transmitter (Panel [ B]). 

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