Receptors for acetylcholine

Acetyichoiine Muscarine is an agonist at muscarinic acetylcholine receptors, for which the receptor was named. It is not certain what role this plays in the psychoactive effects of amanita. 

Muscarinic acetylcholine receptors a class of acetylcholine receptors for which muscarine is the iconic agonist. 

The receptors for acetylcholine, GABA, glycine and serotonin have a homologous structure and form a superfamily. The best-investigated representative of this superfamUy is the nicotinic acetylcholine receptor, for which extensive biochemical and structural data are available. The nicotinic acetylcholine receptor can be treated as a representative of the other receptors of the superfamUy since it can be assumed that the structure-function principles of this receptor apply to the others. 

Neuromuscular junctions can be visualized by light microscopy following labeling of the presynaptic nerve terminal and the postsynaptic acetylcholine receptors. For best results, muscles should be prepared for longitudinal sections, and NMJs in an en face orientation can be imaged. In almost all muscles, the end plate band is near the middle of the muscle and this represents the region of interest. 

Nicotinic acetylcholine receptor The biosensors were constructed with poly (vinylbutyral) membranes incorporating nicotinic acetylcholine receptor for the determination of ACh. The detection range was 0.1-10 pM acetylcholine. [105]... 

Neuromuscular transmission is mediated by nicotinic acetylcholine receptors, for which various subtypes are described (Sargent 1993 McGehee and Role 1995 Karlin and Akabas 1995 Alexander et al. 2001). 

Neurotransmission is based on the secretion of neurotransmitters from secretory vesicles in the presynaptic membrane and the binding of the agonists by receptors on the postsynaptic membrane. The transmitters have to travel only about 20 nm across the synaptic cleft, whereas neurohormones may act on much more distant receptors. The biogenesis of the secretory vesicles and the receptors are intimately connected with the secretory pathway of the eukaryotic cells. In this system a series of membrane-bound structures mediate the transfer of exported proteins from their site of synthesis at the rough endoplasmic reticulum to their site of discharge at the plasma membrane. We will use the chromaffin granules (storage vesicles of the adrenal medulla) as an example for secretory vesicles, and the acetylcholine receptor for receptors of neurotransmitters. 

Wishka, D. G., Walker, D. R, Yates, K. M. et al. Discovery of N-[(37 )-l-azabicyclo [2.2.2]oct-3-yl]furo[2,3-c]pyridine-5-carboxamide, an agonist of the al nicotinic acetylcholine receptor, for the potential treatment of cognitive deficits in schizophrenia synthesis and stmcture-activity relationship. J. Med. Chem. 2006, 49, 4425 436. 

Ziebell, M. R., Nirthanan, S., et al. (2004). Identification of binding sites in the nicotinic acetylcholine receptor for [3H]azietomidate, a photoactivatable general anesthetic. The Journal of Biological Chemistry, 279(17), 17640-17649. 

Natural tropane type compounds causing such effects are hyoscyamine/atropine, 6(3-hydroxyhyoscyamine (anisodamine), anisodine, and scopolamine. They are still today important drugs (Liu et al. 2005) though their semisynthetic derivatives are meanwhile even more important. Traditionally they were called parasympatholytics. Nowadays, they are termed competitive inhibitors (of all known types) of muscarinic acetylcholine receptors (for details see Sect. 3.3.6). As SchmeUer et al. (2000) could demonstrate, such tropane alkaloids do not interfere only with these types of neuroceptors but also bind to the nicotinic ones albeit with much lower affinities. This was determined not only for atropine and scopolamine but also with similar affinities for their intermediates/congeners littorine, 6P- and P-hydroxy-hyoscyamine. However, semisynthetic quaternary compounds like the A/-methyl derivatives of atropine and scopolamine were found to show the highest binding. 

Mode of Action. All of the insecticidal carbamates are cholinergic, and poisoned insects and mammals exhibit violent convulsions and other neuromuscular disturbances. The insecticides are strong carbamylating inhibitors of acetylcholinesterase and may also have a direct action on the acetylcholine receptors because of their pronounced stmctural resemblance to acetylcholine. The overall mechanism for carbamate interaction with acetylcholinesterase is analogous to the normal three-step hydrolysis of acetylcholine however, is much slower than with the acetylated enzyme. 

Elucidation of the stmctural requirements for dmg interaction at the recognition site is by the study of stmcture—activity relationships (SAR), in which, according to a specific biologic response, the effects of systematic molecular modification of a parent dmg stmcture are determined. Such studies have permitted the classification of discrete classes of pharmacological receptors. For example, the neurotransmitter acetylcholine acts at both peripheral and central receptors which are of at least three distinct types. The effects of acetylcholine are mimicked in smooth and cardiac muscles and secretory... 

Antagonists of muscarinic acetylcholine receptors had widely been used since 1860 for the treatment of Parkinson s disease, prior to the discovery of l-DOPA. They block receptors that mediate the response to striatal cholinergic interneurons. The antiparkinsonian effects of drugs like benzatropine, trihexyphenidyl and biper-iden are moderate the resting tremor may sometimes respond in a favorable manner. The adverse effects, e.g., constipation, urinary retention, and mental confusion, may be troublesome, especially in the elderly. 

Also, the outcome covers a large spectrum. Autoantibodies can specifically block an important protein (such as the gastric intrinsic factor required for the uptake of orally taken vitamin B12), or the receptor for —> acetylcholine (as in myasthenia gravis), but also can... 

Curare is a generic term for various South American arrow poisons. Curare has been used for centuries by the Indians along the Amazon and Orinoco rivers for immobilizing and paralyzing wild animals used for food. Preparations of curare are derived from Strychnos species, which contain quaternary neuromuscular alkaloids like tubocurarine. Tubocurarine is a potent antagonist at the nicotinic acetylcholine receptor. 

Lanzafame A A, Christopoulos A, Mitchelson F (2003) Cellular signaling mechanisms for muscarinic acetylcholine receptors. Recept Chann 9 241-260... 

The open channel has in most cases a selective permeability, allowing a restricted class of ions to flow,for example Na+, K+, Ca++ or Cl- and, accordingly, these channels are called Na+-channels, K+-channels, Ca -channels and Cr-channels. In contrast, cation-permeable channels with little selectivity reject all anions but discriminate little among small cations. Little is known about the structures and functions of these non-selective cation channels [1], and so far only one of them, the nicotinic acetylcholine receptor (nAChR, see Nicotinic Receptors), has been characterized in depth [2, 3]. The nAChR is a ligand-gated channel (see below) that does not select well among cations the channel is even permeable to choline, glycine ethylester and tris buffer cations. A number of other plasma... 

The AMPA receptors for glutamate, the nicotinic acetylcholine receptor and the 5-HT3-receptor for serotonin are cation channels (Table 1). When they open, the major consequence is a sudden entry of Na+, depolarization and an excitatory postsynaptic potential (EPSP Fig. 1). 

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