Acetylcholine interaction with membrane receptors

Succinylcholine, similar to acetylcholine, interacts with the cholinergic receptors at the end plate region of the muscle, resulting in depolarization of the chemically excitable membrane. This, in turn, creates local action potentials, spreading them to and depolarizing the adjacent excitable membranes, finally culminating in a muscle contraction, or fasciculation, which is an uncoordinated muscle contraction. However, unlike acetylcholine, succinylcholine is not metabolized by acetylcholinesterase, and hence causes persistent depolarization of the end plate. The continuous presence of succinylcholine leads to inexcitability of the membrane adjacent to the end plate, resulting in... 

It is doubtful that a majority of receptors will ever be isolated and purified to the level of the nicotinic acetylcholine receptor. Even then some important characteristics that the receptor exhibits when embedded in the membrane surrounded by its various ancillary protein and lipid components are lost. Thus studying drug interactions with such receptor isolates will yield limited, possibly erroneous, information to the drug designer. Effects resulting from such interactions on cells, tissues, or organs cannot be evaluated. 

At the neuromuscular junction, acetylcholine interacts with receptors on the muscle end-plate. The resultant depolarization triggers an action potential which is similar to a nervous impulse (described above). For about one millisecond, acetylcholine opens channels that allow sodium ions to flow inwards, there is a temporary loss of membrane potential, and the muscle begins to contract. The acetylcholine is then destroyed by acetylcholinesterase, which is located elsewhere in the end-plate. This process occupies only a few milliseconds and can be reproduced by administering acetylcholine close to the end-plate region. However, injection directly into the interior of the muscle cell produces neither depolarization nor contraction. 

In the case of a stimulus, acetylcholine is released from presynaptic vesicles (exocytosis) into the synaptic cleft and diffuses in fewer than 100 ps to the membrane of a postsynaptic target cell, where it interacts with its receptor (Fig. 8.41). 

Eldefrawi, A.R. and Eldefrawi, M.E.. Phencyclidine interactions with the ionic channel of the acetylcholine receptor and electrogenic membrane. Proc Natl Acad Sci USA 77 1224-1228,... 

There are more than 10 billion neurons that make up the human nervous system, and they interact with one another through neurotransmitters. Acetylcholine, a number of biogenic amines (norepinephrine, dopamine, serotonin, and in all likelihood, histamine and norepinephrine), certain amino acids and peptides, and adenosine are neurotransmitters in the central nervous system. Amino acid neurotransmitters are glutamic and aspartic acids that excite postsynaptic membrane receptors of several neurons as well as y-aminobutyric acid (GABA) and glycine, which are inhibitory neurotransmitters. Endorphins, enkephalins, and substance P are considered peptidergic transmitters. There are many compounds that imitate the action of these neurotransmitters. 

Many different receptor types are coupled to G proteins, including receptors for norepinephrine and epinephrine (a- and p-adrenoceptors), 5-hydroxytrypta-mine (serotonin or 5-HT receptors), and muscarinic acetylcholine receptors. Figure 2.1 presents the structure of one of these, the uz-adrenoceptor from the human kidney. All members of this family of G protein-coupled receptors are characterized by having seven membrane-enclosed domains plus extracellular and intracellular loops. The specific binding sites for agonists occur at the extracellular surface, while the interaction with G proteins occurs with the intracellular portions of the receptor. The general term for any chain of events initiated by receptor activation is signal transduction. 

Reconstitution and bilayer studies provided evidence that the four subunit receptor contains, not only the binding sites for acetylcholine but also the active cation channel, and the activated receptor by itself brings about the response of agonist-induced membrane permeability [50,51]. This is different from the -adrenergic receptor in which the receptor must interact with another membrane protein in order to transmit the signal. 

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