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1 Psych 115 Lecture 7: Acetylcholine and amino acid neurotransmitters Lecture 7: ACh Objectives Describe how Acetylcholine (ACh) is synthesized. Describe the sources for the Acetyl CoA and Choline used for ACh synthesis and indicate what the rate-limiting step is for ACh synthesis. Explain the role for VAChT in ACh neurotransmission and provide the name of an antagonist Explain the role of acetylcholinesterase (AChE) in terminating ACh activity, describe the factors regulating it and describe the neurochemical and behavioral effects of inhibition Compare and contrast muscarinic and nicotinic receptors in terms of their effectors systems and distribution and provide examples of agonists and antagonists of each Explain the structure of the nicotinic receptor and how it can give rise to at least 9 different subtypes. Describe the general structure of mAChRs Explain and illustrate how drugs may interfere with ACh activity by effecting its synthesis, release, degradation or receptor activity and what would be the predicted outcome for each. Explain why atropine can ameliorate the effects of AChE inhibitors. Acetylcholine (ACh) The first neurotransmitter to be discovered (Otto Loewi, 1921) The nicotinic ACh receptor was the first receptor to be discovered (Dale) Very flexible molecule and it adopts different conformations when bound to different ACh receptor subtypes Cholinergic pathway: CNS Acetylcholine is widely distributed in the peripheral and central nervous system . In the CNS, cholinergic neurons can be divided to several groups. : Main groups of ACh groups and pathways in the CNS 1. Interneurons within striatal complex; regulated by glutamate and dopamine 2. Basal forebrain (including nucleus basalis, medial septal nucleus, substantia inominata); source of projection neurons to limbic system and cortex
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2 Cholinergic pathway: PNS Motor systems Cholinergic neurons are found in the spinal ventral horn and in cranial nerves 3-7 and 12. Thus, ACh is secreted in all neuromuscular junctions and stimulates muscle contraction. Autonomic nervous system The principle transmitter by the parasympathetic and sympathetic pregangalionic fibers. Released by most of the parasympathetic post ganglionic innervating glands and smooth muscles which will be excited or inhibited depending on the type of receptor they present. Sources of Acetyl CoA and choline ACh synthesis ACh is synthesized in the cytoplasm from Acetyl CoA and choline in a reaction catalyzed by the enzyme choline acetyltransferase (ChAT) . Factors regulating ACh synthesis : negative feedback : ACh binds to ChAT and inhibits its catalytic ability. Law of mass action : ACh concentration is proportional to the availability of Acetyl CoA, choline and ChAT The most important limiting factor is the rate of choline high affinity uptake . Drugs inhibiting Ach synthesis
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