Muscarinic cholinergic binding sites

Batra S (1990) Interaction of antiestrogens with binding sites for muscarinic cholinergic drugs and calcium channel blockers in cell membranes. Cancer Chemother Pharmacol 26 310-312... 

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... 

Araujo DM, Lapchak PA, Quirion R (1991) Heterogeneous bindingof [ H]4-DAMP to muscarinic cholinergic sites in the rat brain Evidence from membrane binding and autoradiographic studies. Synapse, 9, 165-176. 

Watson, M. et ah, 1986. pH]Pirenzepine and (-)-[ H]quinuclidinyl benzilate binding to rat cerebral cortical and cardiac muscarinic cholinergic sites I. Characterization and regulation of agonist binding to putative muscarinic subtypes. J. Pharmacol. Exp. Ther. 237, 411-418. 

The muscarinic cholinergic system has quite a different mode of operation in that the receptor is connected to the final action by a chain of events. Thus its response is slower than the nicotinic, where the receptor and ion channel are closely connected. Five distinct muscarinic receptors have been identified in mammals, based on anatomical location, genetic analysis, function, and amino acid sequence. All of them have seven transmembrane domains [166, 167, 168, 169]. The N- terminal domain outside the cell binds acetylcholine or other ligands at a site that includes an aspartate residue, while the C-terminal domain inside the cell is coupled to a so-called G-protein , which is initially bound to guanosine diphosphate (GDP), but exchanges it for guanosine triphosphate (GTP) when activated by its transmitter. The activated G-protein then activates phospholipase C, which hydrolyzes phosphoinositides to release 1,4,5-inositol triphosphate [170]. The final action depends on which type of cell is involved so that in some types ion channels are opened just as with the nicotinic receptor, but in other cases other processes are affected, for example the release of dopamine [171]. Since there are these differences... 

Tropane alkaloids are compounds known as muscarinic receptor antagonists. Atropine, its best-known member, and a number of other compounds, block the action of the neurotransmitter acetylcholine on post-ganglionic cholinergic nerves of the parasympathetic nervous system, essentially by blocking its binding to muscarinic cholinergic receptors, whereas they are much less potent at nicotinic receptor sites. 

A search for muscarinic cholinergic function has shown the presence of high affinity binding sites for iV-methylscopolamine (NMS) in homogenates of C. elegans (130). A... 

Wamsley, J. K., Zarbin, M. A., Birdsall, N, J. M., and Kuhar, M. J., 1980, Muscarinic cholinergic receptors autoradiographic localization of high- and low-affinity agonist binding sites, Brain Res. 200 1-12. 

---