Acetylcholine cell-surface

Muscarinic acetylcholine receptors (mAChRs) form a class of cell surface receptors that are activated upon binding of the neurotransmitter, acetylcholine. Structurally and functionally, mAChRs are prototypical members of the superfamily of G protein-coupled receptors. Following acetylcholine binding, the activated mAChRs interact with distinct classes of heterotrimeric G proteins resulting in the activation or inhibition of distinct downstream signaling cascades. 

The neurotransmitter acetylcholine (ACh) exerts its diverse pharmacological actions via binding to and subsequent activation of two general classes of cell surface receptors, the nicotinic and the mAChRs. These two classes of ACh receptors have distinct structural and functional properties. The nicotinic receptors,... 

Although NO does not itself use a G-protein for signalling, the mechanism of NO production in vascular endothelium is initiated by IP3 via a G-protein-linked acetylcholine receptor on the cell surface. The IP3 causes activation of nitric oxide synthase via calcium- calmodulin and the NO generated diffuses from the endothelial cell into the adjacent smooth muscle cell where cGMP is produced. 

Beside this there are some major differences with the neurotransmission in the autonomous nervous system The contractile activity of the skeletal muscle is almost completely dependent on the innervation. There is no basal tone and a loss of the innervation is identical to a total loss in function of the particular skeletal muscle. In contrast to the target organs of the parasympathetic nervous system the skeletal muscle cells only have acetylcholine receptors at the site of the so-called end-plate, the connection between neuron and muscle cell with the rest of the cell surface being insensitive to the transmitter. The release of acetylcholine results in a postjunctional depolarization which is either above the threshold to induce an action potential and a contraction or below the threshold with no contractile response at all. In contrast to the graduated reactions of the parasympathetic target organs, this is an all or nothing transmission. 

The AChR is one of the best characterized of all cell-surface receptors for hormones or neurotransmitters (Figure 2-9). One form of this receptor is a pentamer made up of four different polypeptide subunits (eg, two chains plus one B, one 7, and one 5 chain, all with molecular weights ranging from 43,000 to 50,000). These polypeptides, each of which crosses the lipid bilayer four times, form a cylindrical structure that is 8 nm in diameter. When acetylcholine binds to sites on the subunits, a conformational change occurs that results in the transient opening of a central aqueous channel through which sodium ions penetrate from the extracellular fluid into the cell. 

NO synthase is activated in response to Ca2+, which is released in the endothelial cells in response to acetylcholine or bradykinin interaction with their respective cell surface receptors. The NO synthesized diffuses into smooth muscle cells of the blood vessels causing them to relax. Nitroglycerin, a drug used to treat angina pectoris patients, causes vasodilation by giving rise to NO. 

Steinbach, J.H. "Activation of nicotinic acetylcholine receptors" Cotman, C.W., Poste, G. Nicholson, G.L. Eds. Cell surface and neuronal function, Elsevier/North Holland, New York, 1980, p.119-151. 

Nicotinic acetylcholine receptors (nAChRs) are a family of ligand-gated ion channels that are found in abundance at the neuromuscular junction, and are widely distributed throughout the central and peripheral nervous systems. They comprise five subunit proteins that combine to form a cation permeable pore at the cell surface. In neuronal tissues, multiple nAChR subtypes may be assembled from a diverse array of subunits (a2-a9 32-p4) and their... 

Inhibitors of ADPRT activity reversibly block both muscle cell fusion and the rise in creatine phosphokinase activity associated with this cell differentiation. Myoblast fusion is inhibited in a concentration-dependent manner in the continuous presence of either 3-aminobenzamide or 3-methoxybenzamide (Fig. 6a). These inhibitors do not inhibit proliferation of myoblasts (Fig. 6b). The non-inhibitory analogues, 3-amino-benzoate and 3-methoxybenzoate caused no significant inhibition of fusion at corresponding concentrations (Fig. 6a). Inhibitors of nuclear ADPRT not only block myoblast fusion (Fig. 7a), but they also prevent the usual increase in creatine phosphokinase activity (Fig. 7b). Both the inhibition of cell fusion and of the increase in creatine phosphokinase activity by ADPRT inhibitors, is reversible (Fig. 7a,b). Inhibitors of ADPRT activity also inhibit the appearance of acetylcholine receptors on the muscle cell surface. 

If the major site of acetylcholine-stimulated phosphatidylinositol breakdown in the pancreas is the rough endoplasmic reticular membranes rather than at the cell surface, then it is necessary to postulate that some second messenger system is needed to carry the information from the receptor at the cell surface to the site of the response. The nature of this is not known. The dibutyryl derivatives of cyclic AMP and cyclic GMP do not give rise to phosphatidylinositol breakdown in the pancreas nor does the influx of Ca ion... 

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