Acetylcholinesterase receptor binding

Woodruff-Pak DS, Vogel RW 3rd, Wenk GL. (2001) Galantamine Effect on nicotinic receptor binding, acetylcholinesterase inhibition, and learning. Proc Natl Acad Sci USA 98 2089-2094. 

Correct answer = A. Pilocarpine is used in glaucoma where it is the treatment of choice for the acute attack. It is not cleaved by acetylcholinesterase. It binds mainly to muscarinic receptors, and can enter the brain. Pilocarpine is... 

Inhibits acetylcholinesterase and butyrylcholinesterase activity Inhibits muscarinic and nicotinic receptor binding... 

Figure 14.13 The kinetic sequence of reactions that control the cyclic AMP concentration, and its binding to the effector system, and the kinetic sequence that controls the concentration of a neurotransmitter and its binding to the receptor on the postsyn-aptic membrane. Processes (1) are reactions catalysed by adenyl cyclase, and exocytosis. Reactions (2) are catalysed by phosphodiesterase and, for example, acetylcholinesterase. Reactions (3) are the interactions between the messenger and the effector system both the latter are equilibrium binding processes. (See Chapter 12 (p. 266) for discussions of equilibrium binding.)...

Neuromuscular transmission (B) of motor nerve impulses to the striated muscle fiber takes place at the motor endplate. The nerve impulse liberates acetylcholine (ACh) from the axon terminal. ACh binds to nicotinic cholinocep-tors at the motor endplate. Activation of these receptors causes depolarization of the endplate, from which a propagated action potential (AP) is elicited in the surrounding sarcolemma. The AP triggers a release of Ca from its storage organelles, the sarcoplasmic reticulum (SR), within the muscle fiber the rise in Ca concentration induces a contraction of the myofilaments (electromechanical coupling). Meanwhile, ACh is hydrolyzed by acetylcholinesterase (p. 100) excitation of the endplate subsides. if no AP follows, Ca + is taken up again by the SR and the myofilaments relax. 

Therapeutic measures include 1. administration of atropine in high dosage to shield muscarinic acetylcholine receptors and 2. reactivation of acetylcholinesterase by obidoxime, which successively binds to the enzyme, captures the phosphate residue by a nucleophilic attack, and then dissociates from the active center to release the enzyme from inhibition. 

Substances that block the serine residue in the active center of acetylcholinesterase [2j—e.g., the neurotoxin E605 and other organophosphates—prevent ACh degradation and thus cause prolonged stimulation of the postsynaptic cell. This impairs nerve conduction and muscle contraction. Curare, a paralyzing arrow-poison used by South American Indians, competitively inhibits binding of ACh to its receptor. 

ACh diffusing across the synaptic cleft may bind to ACh receptors (AChRs) to produce an electrical response, interact with acetylcholinesterase (AChE) and be hydrolyzed, or diffuse into the systemic circulation. 

Neuromuscular transmission. Transmitter release at the motor nerve terminal occurs by exocytosis of synaptic vesicles that contain acetylcholine (ACh). The process is enhanced by an action potential that depolarizes the membrane and allows Ca++ entry through channels at the active sites. ACh may be hydrolyzed by acetylcholinesterase (AChE) or bind to receptors (AChRs) located at the peaks of the subsynaptic folds. Simultaneous activation of many AChRs produces an end plate current, which generates an action potential in the adjacent muscle membrane. 

M.B. Skaddan, M.R. Kilbourn, S.E. Snyder, P.S. Sherman, Acetylcholinesterase inhibition increases in vivo N-(2-[ F]fluoroethyl)-4-piperidyl benzilate binding to muscarinic acetylcholine receptors, J. Cereb. Blood Flow Metab. 21 (2001) 144-148. 

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