Cholinergic receptors presynaptic

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... 

Acetyichoiine Ginkgo enhances release of acetylcholine and alters cholinergic receptors. Both direct in vitro application and long-term oral administration increases presynaptic uptake of choline in hippocampal synaptosomes (Kristofikova et al. 1992). The effective concentrations for... 

Schwartz RD, Lehmann J, Kellar KJ Presynaptic nicotinic cholinergic receptors labeled by [3H]acetylcholine on catecholamine and serotonin receptors in brain. J Neurochem 42 1495-1498, 1984... 

ACh acts at two different types of cholinergic receptors Muscarinic and Nicotinic receptors. Muscarinic receptors (1) bind ACh as well as other agonists (muscarine, pilocarpine, bethan-echol) and antagonists (atropine, scopolamine). There are at least 5 different types of muscarinic receptors (M1-M5) and all have slow response times. They are coupled to G-proteins and a variety of second messenger systems. When activated, the final effect can be an opening or closing of channels for K", Ca ", or Cl . Presynaptic cholinergic receptors are of the muscarinic or nicotinic type and can modulate the release of several neurotransmitters. 

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]). 

Pre- and postsynaptic elements, therefore, play a key role in excitation of the brain. We focus here on prototypes of a presynaptic and a postsynaptic element. As an example of a presynaptic element, we selected the dihydropyr-idine-sensitive calcium channel, a member of the superfamily of voltage-gated channel proteins. The most extensively studied membrane protein, the nicotinic cholinergic receptor, which belongs to the family of ligand-gated channels, is present in the postsynaptic membrane. These two examples are used to describe a strategy that aims to identify sequence-specific motifs that are responsible for the performance of unique functions and to outline an experimental approach to evaluate identified structural motifs. 

Thus, flatworm cholinergic receptors display a mixture of nicotinic and muscarinic properties (10, 11, 17, 30, 32) and are therefore pharmacologically different from the classical vertebrate cholinergic receptors. (Nicotine and muscarine have been used classically in vertebrate pharmacology to define two different classes of cholinergic receptors.) These pharmacological differences may be due to a number of factors lack of specificity of vertebrate blockers for flatworm receptors, the presence of a variety of cholinergic receptors on the same or different cells (neuron and/or muscle), activation of multicomponent pathways (e.g., activation of excitatory neuronal input to inhibitory fibers presynaptic to muscle), etc. 

AChE is located strategically within the synapse to exert tight control over cholinergic neurotransmission, Because AChE is one of the most active of all enzymes (each molecule can hydrolyze approximately 5000 molecules of ACh per second) (Cooper el al., 2003), ACh molecules have a very short half-life in the synapse and a consequent transient ability to activate cholinergic receptors. Upon hydrolytic cleavage of the ACh molecule, chtiliuc and acetic acid are released into the synaptic space, after which choline is transported effectively back into the presynaptic terminal by a HACU process, ACh is therefore panially recycled, increasing metabolic efficiency. 

Acetylcholine in the synapse can bind with cholinergic receptors on the postsynaptic or presynaptic membranes to produce a response. Free acetylcholine that is not bound to a receptor is hydrolyzed by AChE. This hydrolysis is the physiologic mechanism for terminating the action of acetylcholine. Enough AChE is present in the synapse to hydrolyze approximately 3 x 10° molecules of acetylcholine in 1 millisecond thus, adequate enzyme activity exists to hydrolyze all the acetylcholine (-3 x 10° molecules) released by one action potential. A number of useful therapeutic cholinomimetic agents have been developed based on the ability of the compounds to inhibit AChE these agents are addressed later in this chapter. 

No overall reduction in cholinergic muscarinic receptors was found but recent studies with relatively specific ligands show a loss of presynaptic M2 receptors, in keeping with the loss of terminals, but no reduction in postsynaptic Mi receptors. Some acetylcholinesterase is found in plaques. 

Despite the paucity of nicotinic receptors in the brain there is considerable evidence that AzD is less common among smokers. Whether this is due to the action of inhaled nicotine is uncertain, but nicotine is known to stimulate presynaptic receptors on cholinergic nerve terminals which, unlike the muscarinic ones, result in increased ACh release. 

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