Cholinergic receptors acetylcholine binding

Glennon, R.A., Dukat, M., 1999b. Nicotine analogs structure-affinity relationships for central acetyl-cholinergic receptor binding. In Yamamoto, I., Casida, J.E. (Eds.), Nicotinoid Insecticides and the Nicotinic Acetylcholine Receptor. Spinger-Verlag, Tokyo, 237-252. 

Acetylcholine is a neurohormone that enhances peristalsis, wakefulness, and memory and is essential for nerve transmission. A deficiency of brain cell receptors that bind acetylcholine—cholinergic receptors—contributes to the characteristic loss of memory in Alzheimer s disease. Cholinergic receptors are structurally similar to those that bind histamine. Therefore, antihistamines and cholinergic agents show overlapping activities. As a result, the antihistamine diphenhydramine has been used to treat insomnia and to combat motion sickness. 

Acetylcholine Binds to cholinergic receptor, which are of two types— muscarinic and nicotinic. 

Paton WDM, Zaimis EJ (1949) The pharmacological actions of polymethylene bistrimethylammo-nium salts. Br J Pharmacol Chemother 4 381 00 Patrick J, Stallcup WB (1977) a-Bungarotoxin binding and cholinergic receptor function on a rat sympathetic nerve line. J Biol Chem 252 8629-8633 Patrick J, Boulter J, Deneris E, Wada K, Wada E, Connolly J, Swanson L, Heinemann S (1989) Structure and function of neuronal nicotinic acetylcholine receptors deduced from cDNA clones. Prog Brain Res 79 27-33... 

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. 

Acetylcholine acts at two different types of cholinergic receptors [see (1) and (2) in Fig. 2.5]. Muscarinic receptors bind ACh as well as other agonists (muscarine, pilocarpine, bethanechol) and antagonists (atropine, scopolamine). There are at least five different types of muscarinic receptors (M1-M5). 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 to open or close channels for K, Ca ", or CL (Bonner, 1989). Nicotinic receptors are less abundant than the muscarinic type in the CNS. They bind ACh as well as agonists such as nicotine or an-... 

Whitehouse PJ, Price DL, Clark AW, et al Alzheimer disease evidence for selective loss of cholinergic neurons in the nucleus basahs. Ann Neurol 10 122-126, 1981 Whitehouse PJ, Price DL, Struble RG, et al Alzheimer s disease and senile dementia—loss of neurons in the basal forebrain. Science 215 1237-1239, 1982 Whitehouse PJ, Hedreen JC, White CL, et al Basal forebrain neurons in dementia of Parkinson s disease. Ann Neurol 13 243-248, 1983 Whitehouse P, Martino A, Antuono P, et al Nicotinic acetylcholine binding sites in Alzheimer s disease. Brain Res 371 146-151, 1986 Whitehouse PJ, Martino AM, Marcus KA, et al Reductions in acetylcholine and nicotine binding in several degenerative diseases. Arch Neurol 45 722-724, 1988 Whitton PS, Sama GS, O Connell MT The effect of the novel antidepressant tianeptine on the concentration of 5-hydroxytryptamine in rat hippocampal diasylates in vivo. Neuropharmacology 39 1-4, 1991 Whitworth P, Kendall DA Lithium selectively inhibits muscarinic receptor-stimulated inositol tetrakisphosphate accumulation in mouse cerebral cortex slices. J Neurochem 51 258-265, 1988... 

As do most neuronal systems, cholinergic receptors show multiplicity, and we distinguish between nicotinic and muscarinic receptors, which differ in many respects. Whereas acetylcholine (4.1) binds to both types of receptors, the plant alkaloids nicotine (4.2) and muscarine (4.3) trigger a response only from nicotinic or muscarinic cholinergic receptors, respectively. Nicotinic receptors are found in all autonomic ganglia (i.e., in the sympathetic system as well as the parasympathetic) and at the neuromuscular endplate of striated muscle. Muscarinic receptors occur at postganglionic... 

Acetylcholine (ACh) is an example of an endogenous neurotransmitter that binds to more than one receptor type, the nicotinic acetylcholine receptor (nAChR) which preferentially binds nicotine and the muscarinic receptor which binds muscarine, a mushroom alkaloid. The latter is a G protein-coupled receptor while the nACh receptor is an excitatory ligand-gated ion channel that transports Na-i- ions. Nicotinic cholinergic receptors are found in the CNS, autonomic ganglia, and at the neuromuscular junction of skeletal muscles. They are a possible target for anaesthetics. 

Cholinergic receptors are subdivided into two categories nicotinic and muscarinic. Although acetylcholine will bind to all cholinergic receptors, certain receptors bind preferentially with the drug nicotine. Other receptors have a specific affinity for muscarine, a naturally occurring compound found in certain poisonous mushrooms. Thus the terms nicotinic and muscarinic were derived. 

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. 

After release from the presynaptic terminal, acetylcholine molecules may bind to and activate an acetylcholine receptor (cholinoceptor). Eventually (and usually very rapidly), all of the acetylcholine released will diffuse within range of an acetylcholinesterase (AChE) molecule. AChE very efficiently splits acetylcholine into choline and acetate, neither of which has significant transmitter effect, and thereby terminates the action of the transmitter (Figure 6-3). Most cholinergic synapses are richly supplied with acetylcholinesterase the half-life of acetylcholine in the synapse is therefore very short. Acetylcholinesterase is also found in other tissues, eg, red blood cells. (Another cholinesterase with a lower specificity for acetylcholine, butyrylcholinesterase [pseudocholinesterase], is found in blood plasma, liver, glia, and many other tissues.)... 

Acetylcholine (9.12) binds both types of cholinergic receptors muscarinic and nicotinic (Figure 9.9). The names of these receptor types were based on muscarine (9.13) and nicotine (9.14), selective agonists for each receptor. A muscarinic response is characterized by nausea, salivation, and tearing. Nicotinic responses are noted by an acceleration of the heart rate. Acetylcholine s ability to elicit a response from both subtypes of receptors may imply that different conformations of acetylcholine may be responsible for binding to each receptor. 

The effects of curare develop rapidly after it enters the body. Victims develop rapid weakness of voluntary muscles followed by paralysis, respiratory failure, and death. The cause is a blockade of nicotinic cholinergic receptors at the neuromuscular junctions in skeletal muscle. Unlike botulinum toxin, release of acetylcholine by the cholinergic nerve terminals is not affected. When curare is present, however, the acetylcholine that is released cannot bind to the receptors because they are reversibly occupied by the curare. As a consequence, nerve-muscle communication fails and paralysis ensues. 

Neurotransmission in adrenergic neurons closely resembles that already described for the cholinergic neurons (p. 37), except that norepinephrine is the neurotransmitter instead of acetylcholine. Neurotransmission takes place at numerous beadlike enlargements called varicosities the process involves five steps the synthesis, storage, release, and receptor binding of the norepinephrine, followed by removal of the neurotransmitter from the synaptic gap (Figure 6.3). 

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