Muscarinic receptors activation

Many measurements in pharmacology rely on a chain of events following receptor activation to produce a measurable response — for example, contraction of the smooth muscle of a piece of guinea-pig ileum in response to muscarinic receptor activation by acetylcholine. This means that the relationship between receptor occupancy and response is likely to be complex, and mechanisms of drug action in such systems are often difficult to define. 

The answer is d. (Hardman, pp 142—M3.) ACh will stimulate both muscarinic and nicotinic receptors. Skeletal muscle contraction is mediated through NM receptors, and ganglionic stimulation is an effect of NN receptors All of the other effects listed in the question occur following muscarinic receptor activation and will be blocked by atropine and scopolamine, both of which are muscarinic receptor antagonists. Skeletal muscle contraction will not be affected by these drugs rather, a neuromuscular blocker (e.g., tubocurarine) is required to antagonize this effect of ACh. 

Muscarinic receptor activation causes inhibition of adenylyl cyclase, stimulation of phospholipase C and regulation of ion channels 203... 

Muscarinic receptor activation causes inhibition of adenylyl cyclase, stimulation of phospholipase C and regulation of ion channels. Many types of neuron and effector cell respond to muscarinic receptor stimulation. Despite the diversity of responses that ensue, the initial event that follows ligand binding to the muscarinic receptor is, in all cases, the interaction of the receptor with a G protein. Depending on the nature of the G protein and the available effectors, the receptor-G-protein interaction can initiate any of several early biochemical events. Common responses elicited by muscarinic receptor occupation are inhibition of adenylyl cyclase, stimulation of phos-phoinositide hydrolysis and regulation of potassium or other ion channels [47] (Fig. 11-10). The particular receptor subtypes eliciting those responses are discussed below. (See also Chs 20 and 21.)... 

Fanelli, F., Menziani, M.C. and De Benedetti, P.G. (1995) Molecular dynamics simulations of m3-muscarinic receptor activation and QSAR analysis. Bioorganic el Medicinal Chemistry, 3, 1465-1477. 

Muscarinic receptor activation of cortical pyramidal cells occurs with a latency of around 250 msec (Taylor 8c Brown, 1999). There is also an approximate 500 msec time lag between the occurrence of a stimulus and consciousness of that stimulus (Libet et ah, 1991). Hence the typical delay associated with muscarinic action (and that of other metabotropic receptors) coincides with the time lag for stimuli reaching consciousness. Thus, cholinergic affer-ents to the cerebral cortex may contribute to 40 Hz activity, as well as to larger envelopes of activity (or inactivity) lasting 250-500 msec. 

Muscarinic receptor activation of an intradendritic site mediating conscious activity... 

H. C. HartzeU (1982). Physiological consequences of muscarinic receptor activation. In J. W. 

The EOs reduced the contraction induced by acetylcholine, histamine [226-228, 210, 225, 232, 233], carbachol (muscarinic receptor activator) [237] and 5-hydroxytryptamine [229]. The EOs were found to relax intestinal smooth muscle by reducing the influx of Ca [227, 234], K+ [210, 224-226, 229, 230] and Ba [229, 237]. However, other reports have shown that lavender and geranium EOs were unlikely to act as cationic channel blockers [232]. The activities of the EOs resembled those of dicyclomine and atropine (muscarinic receptor antagonists) and dihydropyridine (calcium antagonist) by producing smooth-muscle relaxation [225, 236]. 

Zhu L, Yang LM, Cui YY, Zheng PL, Niu YY, Wang H, Lu Y, Ren QS, Wei PJ, Chen HZ (2008) Stereoselectivity of satropane, a novel tropane analog, on iris muscarinic receptor activation and intraocular hypotension. Acta Pharmacol Sin 29 177-184... 

Oyasu H, Yamamoto T, Sato N et al. (1994) Urinary bladder-selective action of the new antimuscarinic compound vamicamide. Arzneim Forsch/Drug Res 44 1242-1249 Peterson JS, Hanson RC, Noronha-Blob L (1989) In vivo cystometrogram studies in urethane-anesthetized and conscious guinea pigs. J Pharmacol Meth 21 231-241 Pietra C, Poggesi E, Angelico P et al. (1990) Effects of some antidepressants on the volume-induced reflex contractions of the rat urinary bladder lack of correlation with muscarinic receptors activity. Pharmacol Res 22 421-432 Postius S, Szelenyi I (1983) In vivo rat bladder a new model to screen spasmolytic compounds. J Pharmacol Meth 9 53-61... 

There are alternative explanations of how the muscarinic receptor activates PI3 kinase. Tong et al.47 propose that the coupling somehow involves receptor internalization as transgenic mutant mice in which receptor internalization was blocked could not be preconditioned. Miura s group proposes that the metalloproteinase liberates TNF rather than EGF.48 In our rabbit cardiomyocyte model, however, the evidence for EGF coupling seems very strong.49... 

Intravenous administration of either one of the four pure compounds previously isolated from M. oleifera leaves (niazinin A, niazinin B, niazimicin and niaziminin A + B) in the concentration range of 1-10 mg/kg, produces hypotensive and bradycardiac effects in anaesthetized rats. Pretreatment of the animals with atropine (1 mg/kg) completely eliminates the hypotensive and bradycardiac effects of acetylchohne (ACh), whereas cardiovascular responses to the test compounds remains unaltered, ruling out the possible involvement of muscarinic receptor activation. In isolated guinea-pig atria all the compounds... 

Following i.p. injections in mice, xanomeline produced signs of muscarinic receptor activity at 1.0 and 10 mg/kg. 

Dilation of vascular beds by exogenous ACh is due primarily to M receptors on endothehal ceUs. Most vessels lack chohnergic innervation, but their endothehal and smooth muscle cehs express muscarinic receptors. In each ceh type, stimulation of the muscarinic receptors activates the G -PLC-IPj pathway and mobilizes ceh Ca +. In endothelial cehs, this leads to Ca +-calmodulin-dependent... 

Acetylcholine has two types of receptors nicotinic ion channel receptors, the receptors inhibited by antibodies in myasthenia gravis, and muscarinic receptors, which exist as a variety of subtypes. The M2 muscarinic receptors activate a Gai/ het-erotrimeric G protein in which release of the Py subunit controls K+ channels and pacemaker activity in the heart. Epinephrine has several types and subtypes of heptahelical receptors p receptors work through a Ga and stimulate adenylyl cyclase 2 receptors in other cells work through a G i protein and inhibit adenylyl cyclase receptors work through Ga, subunits and activate phospholipase Cp. This variety in receptor types allows a messenger to have different actions in different cells. 

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