Binding to acetylcholine receptor

Atropine Sometimes used as an antidote for nerve agents. It inhibits the action of acetylcholine by binding to acetylcholine receptors. 

Mecfianism of Action A cholinergic-receptor agonist that binds to acetylcholine receptors, producing both stimulating and depressant effects on the peripheral and central nervous systems. Therapeutic Effect Provides a source of nicotine during nicotine withdrawal and reduces withdrawal symptoms. 

The third factor is that PAs are extremely effective broad-spectrum feeding deterrents. Numerous species spanning 11 plant families have made use of this attribute (Hartmann and Ober, 2000). Arctiids and other PA-pharmocophagous insects have converted antiherbivore defenses to antipredator defenses. We know little about the mechanisms by which PAs affect their unpalatability. It seems unlikely that the long-term cytotoxic and genotoxic effects of PAs are relevant to their fast-acting deterrency. Recent work has indicated that some PAs bind to acetylcholine receptors (Schmeller et al., 1997) however, further study is required to understand the mode of action of the PAs. 

Nicotine and the neurotransmitter acetylcholine, which acts on maintenance neurons, have similar structures, as Figure 14.28 illustrates. Nicotine molecules are therefore able to bind to acetylcholine receptor sites and trigger many of acetylcholines effects, including relaxation and increased digestion, which... 

ACETYLCHOLINE A chemical that transmits nerve impulses from one nerve fiber to another (neurotransmitter). The pleasurable effects of nicotine are a direct result of nicotine binding to acetylcholine receptors. 

As with the mental effects of nicotine, the physiological effects are brought about by its actions on the nervous system, both peripheral and central. Nicotine changes the transmission of nerve impulses by binding to acetylcholine receptors, and induces the release of several chemical messengers, which in turn affect several body systems. 

The previous discussion of amino acid catabolic disorders indicates that catabolic processes are just as important for the proper functioning of cells and organisms as are anabolic processes. This is no less true for molecules that act as neurotransmitters. To maintain precise information transfer, neurotransmitters are usually quickly degraded or removed from the synaptic cleft. An extreme example of enzyme inhibition illustrates the importance of neurotransmitter degradation. Recall that acetylcholine is the neurotransmitter that initiates muscle contraction. Shortly afterwards, the action of acetylcholine is terminated by the enzyme acetylcholinesterase. (Acetylcholine must be destroyed rapidly so that muscle can relax before the next contraction.) Acetylcholinesterase is a serine esterase that hydrolyzes acetylcholine to acetate and choline. Serine esterases have catalytic mechanisms similar to those of the serine proteases (Section 6.4). Both types of enzymes are irreversibly inhibited by DFP (diisopropylfluorophosphate). Exposure to DFP causes muscle paralysis because acetylcholinesterase is irreversibly inhibited. With each nerve impulse, more acetylcholine molecules enter the neuromuscular synaptic cleft. The accumulating acetylcholine molecules repetitively bind to acetylcholine receptors. The overstimulated muscle cells soon become paralyzed (nonfunctional). Affected individuals suffocate because of paralyzed respiratory muscles. 

In the transmission of nerve impulses across a junction between cellsa synapsethe transmitting cell releases acetylcholine into the synapse. Acetylcholine diffuses to the receiving cell, where it binds to acetylcholine receptor molecules in the membrane of the receiving cell. Acetylcholine is then degraded by acetylcholinesterase, to free the receptors so that they can respond to the next signal. 

Nicotine is an agonist of acetylcholine. An agonist is a compound that binds to the receptor for another compoimd and causes or enhances the biological response. By binding to acetylcholine receptors, nicotine causes the sense of alertness and calm many smokers experience. Nerve cells that respond to nicotine may also signal nerve cells that produce dopamine. As noted above, the dopamine may be responsible for the addictive property of nicotine. 

FIGURE 12 Botulinum toxin causes skeletal muscle paralysis by binding to acetylcholine receptors on the motor end plate. 

The anthelmintic activity of the quinolizidine alkaloids has been reviewed [394]. It is well recognised that quinolizidine alkaloids deter or repel insects and non-insect herbivores [394], These compounds can interfere with protein biosynthesis and some bind to acetylcholine receptors with high affinity. (-)-N-methylcytisine (233) and (-)-anagyrine (234) were isolated from the roots of Sophora flavescens, a plant used in traditional Chinese medicine as an anthelmintic. N-methyl cytisine was twice as active as anagyrine but only half as active as (-)cytisine and nicotine [395,396] The alkaloids (3-6 pg) inhibited reproduction of B. xylophilus in the cotton balls assay. 

Fig. 47.3. Events leading to sarcoplasmic reticulum calcium release in skeletal muscle. 1. Acetylcholine, released at the synaptic cleft, binds to acetylcholine receptors on the sar-colemma, leading to a change of conformation of the receptors such that they now act as an ion pore. This allows sodium to enter the cell and potassium to leave. 2. The membrane polarization that results from these ion movements is transmitted throughout the muscle fiber by the T-tubule system. 3. A receptor in the T-tubules (the dihydropyridine receptor, DHPR) is activated by membrane polarization (a voltage-gated activation) such that activated DHPR physically binds to and activates the ryanodine receptor in the sarcoplasmic reticulum (depolarization-induced calcium release). 4. The activation of the ryanodine receptor, which is a calcium channel, leads to calcium release from the SR into the sarcoplasm. In cardiac muscle, activation of DHPR leads to calcium release from the T-tubules, and this small calcium release is responsible for the activation of the cardiac ryanodine receptor (calcium-induced calcium release) to release large amounts of calcium into the sarcoplasm.

Cobra venom helps the snake secure food by binding to acetylcholine receptors on the diaphragm of a bite victim, leading to the loss of function of the diaphragm muscle tissue and eventually death. In order to develop more potent antivenoms, scientists have studied what happens to the toxin once it has bound the acetylcholine receptors. They have found that the toxin is released from the receptor in a process that can be described by the rate law... 

Areca catechu (Arecaceae, betel nut) is the world s most commonly used masticatory. This palm seed is used in conjunction with Piper betle leaves, Acacia catechu bark, lime, and other accompaniments (Gowda, 1951) by perhaps 1 billion of the world s inhabitants daily. Arecoline (52) is the most commonly studied alkaloid of Areca catechu seeds. This alkaloid has muscarinic action (mimics acetylcholine and binds to acetylcholine receptors) (Wink, 1993). Low doses produce vasodilation and a fall in both systolic and diastolic blood pressure. Arecoline exerts stimulatory effects on the gastrointestinal tract and enhances diaphoresis. Arecoline has an LD50 s.c. of 100 mg/kg in mouse. This alkaloid is a feeding deterrent to certain insects (Wink, 1993). 

Love, R. A. and Stroud, R. M. (1986) The crystal structure of a-bungarotoxin at 2.5 A resolution Relation to solution structure and binding to acetylcholine receptor. Protein Eng. 1 37-46. 

Radding, W., Corfield, RW.R., Levinson, L.S., Hashim, G.A., and Low, B.W., 1988, Alpha-toxin binding to acetylcholine receptor 179-191 peptides - Intrinsic fluorescence studies, FEES Lett. 231 212-216. 

---