muscarine

Summary

Summary: A toxic alkaloid found in Amanita muscaria (fly fungus) and other fungi of the Inocybe species. It is the first parasympathomimetic substance ever studied and causes profound parasympathetic activation that may end in convulsions and death. The specific antidote is atropine.

Top Publications

  1. Canet Aviles R, Anderton M, Hooper N, Turner A, Vaughan P. Muscarine enhances soluble amyloid precursor protein secretion in human neuroblastoma SH-SY5Y by a pathway dependent on protein kinase C(alpha), src-tyrosine kinase and extracellular signal-regulated kinase but not phospholipase C. Brain Res Mol Brain Res. 2002;102:62-72 pubmed
    The signalling pathways by which muscarine and epidermal growth factor (EGF) regulate the secretion of the alpha-secretase cleavage product (sAPPalpha) of the amyloid precursor protein (APP) were examined in the human neuroblastoma SH-..
  2. Jin Z. Muscarine, imidazole, oxazole and thiazole alkaloids. Nat Prod Rep. 2005;22:196-229 pubmed
    ..The isolation, biological activity and total synthesis of naturally occurring muscarine, imidazole, oxazole and thiazole alkaloids have been reviewed...
  3. Jin Z. Muscarine, imidazole, oxazole, and thiazole alkaloids. Nat Prod Rep. 2011;28:1143-91 pubmed publisher
    ..The latest progress in the isolation, biological activities, chemical synthetic studies, and biosynthetic pathways on these natural products is summarized in this review...
  4. Lindgren C, Newman Z, Morford J, Ryan S, Battani K, Su Z. Cyclooxygenase-2, prostaglandin E2 glycerol ester and nitric oxide are involved in muscarine-induced presynaptic enhancement at the vertebrate neuromuscular junction. J Physiol. 2013;591:4749-64 pubmed publisher
    ..nimesulide or DuP 697, prevents the delayed increase in endplate potential (EPP) amplitude normally produced by muscarine. In keeping with its putative role as a mediator of the delayed muscarinic effect, PGE2-G enhances evoked ..
  5. Haberberger R, Scholz R, Kummer W, Kress M. M2-receptor subtype does not mediate muscarine-induced increases in [Ca(2+)](i) in nociceptive neurons of rat dorsal root ganglia. J Neurophysiol. 2000;84:1934-41 pubmed
    ..After 1 day in culture exposure of dissociated medium-sized neurons (20-35 micrometer diam) to muscarine was followed by rises in [Ca(2+)](i) in 76% of the neurons...
  6. Newman Z, Malik P, Wu T, Ochoa C, Watsa N, Lindgren C. Endocannabinoids mediate muscarine-induced synaptic depression at the vertebrate neuromuscular junction. Eur J Neurosci. 2007;25:1619-30 pubmed
    ..a CB(1) antagonist, prevents muscarine from inhibiting release and arachidonylcyclopropylamide (ACPA), a CB(1) receptor agonist, mimics M(3) activation ..
  7. Prakriya M, Solaro C, Lingle C. [Ca2+]i elevations detected by BK channels during Ca2+ influx and muscarine-mediated release of Ca2+ from intracellular stores in rat chromaffin cells. J Neurosci. 1996;16:4344-59 pubmed
    ..This information was used to examine submembrane [Ca2+]i elevations arising out of Ca2+ influx and muscarine-mediated release of Ca2+ from intracellular stores...
  8. Jin Z. Muscarine, imidazole, oxazole and thiazole alkaloids. Nat Prod Rep. 2009;26:382-445 pubmed publisher
    ..In this review, the isolation, biological activities, chemical synthetic studies, and biosynthetic pathways of these natural products are summarized...
  9. Jin Z. Muscarine, imidaozle, oxazole and thiazole alkaloids. Nat Prod Rep. 2013;30:869-915 pubmed publisher
    ..The latest progress involving isolation, biological activities, chemical synthetic studies, and biosynthetic pathways of these natural products has been summarized in this review...

More Information

Publications62

  1. Neely A, Lingle C. Effects of muscarine on single rat adrenal chromaffin cells. J Physiol. 1992;453:133-66 pubmed
    1. The action of muscarine on membrane currents and cytosolic calcium (Ca2+) of dissociated rat adrenal chromaffin cells was investigated using standard whole-cell voltage-clamp techniques and microfluorimetry of unclamped single cells...
  2. Hong W, Werling L. Binding of sigma receptor ligands and their effects on muscarine-induced Ca(2+) changes in SH-SY5Y cells. Eur J Pharmacol. 2002;436:35-45 pubmed
    ..basal levels of intracellular Ca(2+) concentration ([Ca(2+)](i)) in these cells, but they significantly reduced muscarine-induced [Ca(2+)](i) changes in a dose-related manner...
  3. Scroggs R, Cardenas C, Whittaker J, Kitai S. Muscarine reduces calcium-dependent electrical activity in substantia nigra dopaminergic neurons. J Neurophysiol. 2001;86:2966-72 pubmed
    The effect of muscarine on Ca2+ dependent electrical activity was studied in dopamine (DA) neurons located in the substantia nigra pars compacta (SNc) in brain slices from young rats, using sharp electrodes...
  4. Heinrich R, Wenzel B, Elsner N. A role for muscarinic excitation: control of specific singing behavior by activation of the adenylate cyclase pathway in the brain of grasshoppers. Proc Natl Acad Sci U S A. 2001;98:9919-23 pubmed
    ..Coinjections of the muscarinic receptor antagonist scopolamine and periodic stimulations with muscarine identified muscarinic receptor activation as being the basis for the underlying accumulation of excitation...
  5. Graves A, Lewin K, A Lindgren C. Nitric oxide, cAMP and the biphasic muscarinic modulation of ACh release at the lizard neuromuscular junction. J Physiol. 2004;559:423-32 pubmed
    ..The activation of muscarinic ACh receptors generated a biphasic modulation of synaptic transmission. Muscarine-induced activation of M3 receptors (0-12 min) decreased release, whereas M1 activation (> 12 min) enhanced ..
  6. Tavares I, Borrelli F, Welsh N. Inhibition of gastric acid secretion by nimesulide: a possible factor in its gastric tolerability. Clin Exp Rheumatol. 2001;19:S13-5 pubmed
    ..To study the effect of nimesulide on acid secretion in mouse isolated stomach...
  7. Lakey J, Aspinwall C, Cavanagh T, Kennedy R. Secretion from islets and single islet cells following cryopreservation. Cell Transplant. 1999;8:691-8 pubmed
    ..It was determined that beta-cells recovered following cryopreservation are capable of secreting insulin at levels and frequencies comparable to those of cultured nonfrozen islet preparations...
  8. Fanselow E, Richardson K, Connors B. Selective, state-dependent activation of somatostatin-expressing inhibitory interneurons in mouse neocortex. J Neurophysiol. 2008;100:2640-52 pubmed publisher
    ..Because GIN cells are more readily activated than RS and FS cells, it is possible that they act as "first responders" when cortical excitatory activity increases...
  9. Le Ray D, Brocard F, Dubuc R. Muscarinic modulation of the trigemino-reticular pathway in lampreys. J Neurophysiol. 2004;92:926-38 pubmed
    ..The functional significance of a muscarinic modulation of a sensory transmission to reticulospinal neurons is discussed...
  10. Warashina A. Mechanism by which wortmannin and LY294002 inhibit catecholamine secretion in the rat adrenal medullary cells. Cell Calcium. 2001;29:239-47 pubmed
    ..Compared with the high-K(+)-elicited responses, muscarine-evoked Ca-responses and secretory responses were more strongly inhibited by wortmannin, but less affected by ..
  11. Tachikawa E, Kudo K, Harada K, Kashimoto T, Miyate Y, Kakizaki A, et al. Effects of ginseng saponins on responses induced by various receptor stimuli. Eur J Pharmacol. 1999;369:23-32 pubmed
    ..the nicotine-induced secretion of catecholamines from the adrenal chromaffin cells, but it did not affect the muscarine- and the histamine-induced ileum contractions...
  12. Hoshi N, Langeberg L, Gould C, Newton A, Scott J. Interaction with AKAP79 modifies the cellular pharmacology of PKC. Mol Cell. 2010;37:541-50 pubmed publisher
    ..This implies that intracellular binding partners not only couple individual molecular events in a cell signaling process but can also change the pharmacological profile of certain protein kinases. ..
  13. Michel F, Fortin G, Martel P, Yeomans J, Trudeau L. M3-like muscarinic receptors mediate Ca2+ influx in rat mesencephalic GABAergic neurones through a protein kinase C-dependent mechanism. Neuropharmacology. 2005;48:796-809 pubmed
    ..Using a mesencephalic primary culture model, we show here that muscarine (10 microM) increases intracellular Ca2+ concentrations ([Ca2+]i) in GABAergic interneurones...
  14. Reid C, Coleman H, Finkelstein D, Horne M, Drago J. Null mutation of the alpha4 nicotinic receptor subunit increases the propensity of muscarinic-mediated neuronal bursting in mouse hippocampal slices. Neuropharmacology. 2006;51:587-96 pubmed
  15. Cea del Rio C, Lawrence J, Erdelyi F, Szabo G, McBain C. Cholinergic modulation amplifies the intrinsic oscillatory properties of CA1 hippocampal cholecystokinin-positive interneurons. J Physiol. 2011;589:609-27 pubmed publisher
  16. Hirase M, Ono K, Yamashita H, Inenaga K. Central injection of galanin inhibits angiotensin II-induced responses in rats. Neuroreport. 2008;19:323-6 pubmed publisher
    ..These results suggest that galanin inhibits angiotensin II-induced physiological responses...
  17. Aguilar J, Ballesta J, Reig J, Palmero M, Viniegra S, Criado M. Muscarinic receptor subtypes in bovine adrenal medulla. Neurochem Res. 1992;17:1235-9 pubmed
    ..The presence of multiplicity of subtypes in the adrenal medulla membranes suggests a diversity of functions of muscarinic receptors in the adrenal gland...
  18. Hernandez Echeagaray E, Galarraga E, Bargas J. 3-Alpha-chloro-imperialine, a potent blocker of cholinergic presynaptic modulation of glutamatergic afferents in the rat neostriatum. Neuropharmacology. 1998;37:1493-502 pubmed
    ..The administration of both 1 microM carbachol or 20 nM muscarine increased PPF...
  19. Tsai C, Ochillo R. Pharmacological effects of berberine on the longitudinal muscle of the guinea-pig isolated ileum. Arch Int Pharmacodyn Ther. 1991;310:116-31 pubmed
    ..Berberine dose-dependently antagonized the effects of muscarine, a specific muscarinic receptor agonist, in a fashion similar to the antagonism of acetylcholine, providing ..
  20. Hornby T, McDonagh J, Reinking R, Stuart D. Effects of excitatory modulation on intrinsic properties of turtle motoneurons. J Neurophysiol. 2002;88:86-97 pubmed
    ..Responses were noted following application of an excitatory modulator: serotonin (5-HT), muscarine, trans-1-amino-1,3-cyclopentane dicarboxylic acid (tACPD), or all three combined...
  21. Bungardt E, Vockert E, Feifel R, Moser U, Tacke R, Mutschler E, et al. Characterization of muscarinic receptors mediating vasodilation in guinea-pig ileum submucosal arterioles by the use of computer-assisted videomicroscopy. Eur J Pharmacol. 1992;213:53-61 pubmed
    ..in rank order of potency): acetylcholine = arecaidine propargyl ester (APE) greater than oxotremorine = (+/-)-muscarine = (+/-)-methacholine greater than carbachol greater than 4-[[N-(4-chlorophenyl)carbamoyl]oxy]-2-..
  22. Chevallier S, Nagy F, Cabelguen J. Cholinergic control of excitability of spinal motoneurones in the salamander. J Physiol. 2006;570:525-40 pubmed
    ..All of these effects were mimicked by extracellular application of muscarine (20 microM), and blocked by application of the muscarinic receptor antagonist atropine (0.1-1 microM)...
  23. Zhou X, Marley P, Livett B. Substance P modulates the time course of nicotinic but not muscarinic catecholamine secretion from perfused adrenal glands of rat. Br J Pharmacol. 1991;104:159-65 pubmed
    ..effects of SP, perfused at different concentrations, on CA secretion evoked by 10(-5) M nicotine and 10(-4) M muscarine. 3...
  24. Hosli E, Rühl W, Hösli L. Histochemical and electrophysiological evidence for estrogen receptors on cultured astrocytes: colocalization with cholinergic receptors. Int J Dev Neurosci. 2000;18:101-11 pubmed
    ..Furthermore, on the same astrocytes, 17beta-estradiol, muscarine and nicotine caused hyperpolarizations, suggesting a coexistence of receptors for estrogen and the cholinergic ..
  25. Borrelli F, Posadas I, Capasso R, Aviello G, Ascione V, Capasso F. Effect of caffeic acid phenethyl ester on gastric acid secretion in vitro. Eur J Pharmacol. 2005;521:139-43 pubmed
    ..Our results show that CAPE increases gastric acid secretion stimulated by an acetylcholine agonist receptor likely through inhibition of acetylcholinesterase activity...
  26. Cai Y, Chen S, Han H, Sood A, Lopez Berestein G, Pan H. Role of M2, M3, and M4 muscarinic receptor subtypes in the spinal cholinergic control of nociception revealed using siRNA in rats. J Neurochem. 2009;111:1000-10 pubmed publisher
    ..Treatment with the M(2)-siRNA caused a large reduction in the inhibitory effect of muscarine on the nociceptive withdrawal threshold...
  27. Gashi A, Nadel J, Basbaum C. Tracheal gland mucous cells stimulated in vitro with adrenergic and cholinergic drugs. Tissue Cell. 1989;21:59-67 pubmed
    ..Taken together, these data suggest that tracheal mucous cells secrete 35S-labeled macromolecules in response to beta-adrenergic and muscarinic agonists by an exocytotic process that involves a reduction in cell size...
  28. Wenzel B, Kunst M, Günther C, Ganter G, Lakes Harlan R, Elsner N, et al. Nitric oxide/cyclic guanosine monophosphate signaling in the central complex of the grasshopper brain inhibits singing behavior. J Comp Neurol. 2005;488:129-39 pubmed
    ..The nitric oxide-donor sodium nitroprusside caused a reversible suppression of muscarine-stimulated sound production that could be blocked by 1H-[1,2,4]oxadiazolo-[4,3-a]quinoxaline-1-one (ODQ), which ..
  29. Summers S, Ulloa A, Purdy R. Endothelial role in the thoracic aorta response to hindlimb unloading in rats. Aviat Space Environ Med. 2007;78:1103-7 pubmed
    ..Hindlimb unloading (HLU) is used to simulate microgravity in rats and has been shown to decrease contractile response in the abdominal aorta. The thoracic aorta has not been studied as thoroughly...
  30. Wickman K, Nemec J, Gendler S, Clapham D. Abnormal heart rate regulation in GIRK4 knockout mice. Neuron. 1998;20:103-14 pubmed
    ..Interestingly, noncholinergic systems also appear to modulate heart activity through I(KACh). Thus, I(KACh) is critical for effective heart rate regulation in mice...
  31. Hoogduijn M, Cheng A, Genever P. Functional nicotinic and muscarinic receptors on mesenchymal stem cells. Stem Cells Dev. 2009;18:103-12 pubmed publisher
    ..Stimulation of MSCs with the nicotinic receptor agonist nicotine and the muscarinic receptor agonist muscarine induced immediate and transient increases in intracellular Ca(2+) concentration...
  32. Kullmann P, Horn J. Excitatory muscarinic modulation strengthens virtual nicotinic synapses on sympathetic neurons and thereby enhances synaptic gain. J Neurophysiol. 2006;96:3104-13 pubmed
    ..b>Muscarine (1 muM) strengthened the impact of virtual synapses by reducing the artificial nicotinic conductance required to ..
  33. Calderon D, Leverkova N, Peinado A. Gq/11-induced and spontaneous waves of coordinated network activation in developing frontal cortex. J Neurosci. 2005;25:1737-49 pubmed
    ..The findings suggest that a poorly recognized, developmentally regulated form of strong network activation found predominantly in the frontal cortex could potentially exert a profound influence on brain development...
  34. Morita M, Suzuki T. The identification of the sympathetic neurons innervating the hamster submandibular gland and their electrophysiological membrane properties. Bull Tokyo Dent Coll. 2001;42:15-33 pubmed
    ..The delayed rectifiers, A channels, and BK and SK (slowly Ca2+-activated) channels were involved in generation of spike-AHP. Muscarine suppressed the Ca2+ component of spike via muscarinic receptors.
  35. Takayasu Y, Iino M, Furuya N, Ozawa S. Muscarine-induced increase in frequency of spontaneous EPSCs in Purkinje cells in the vestibulo-cerebellum of the rat. J Neurosci. 2003;23:6200-8 pubmed
    ..This effect of ACh was mimicked by muscarine but not by nicotine...
  36. Jin Z, Li Z, Huang R. Muscarine, imidazole, oxazole, thiazole, Amaryllidaceae and Sceletium alkaloids. Nat Prod Rep. 2002;19:454-76 pubmed
    ..references covers the literature from July 2000 to June 2001 on the isolation, bioactivities, and synthetic highlights of complex natural products including muscarine, imidazole, oxazole, thiazole, Amaryllidaceae and Sceletium alkaloids.
  37. Inoue M, Harada K, Matsuoka H, Nakamura J, Warashina A. Mechanisms and roles of muscarinic activation in guinea-pig adrenal medullary cells. Am J Physiol Cell Physiol. 2012;303:C635-44 pubmed publisher
    ..Bath application of muscarine induced an inward current at -60 mV. This inward current was partially suppressed by quinine with an IC(50) of 6...
  38. Hussong J, Lindken R, Faulhammer P, Noreikat K, Sharp K, Kummer W, et al. Cilia-driven particle and fluid transport over mucus-free mice tracheae. J Biomech. 2013;46:593-8 pubmed publisher
    ..In response to muscarine or ATP stimulation, maximum fluid transport rates of 250 ?m/s at 15 ?m distance to the tracheal epithelia were ..
  39. Forsythe I, Lambert D, Nahorski S, Lindsdell P. Elevation of cytosolic calcium by cholinoceptor agonists in SH-SY5Y human neuroblastoma cells: estimation of the contribution of voltage-dependent currents. Br J Pharmacol. 1992;107:207-14 pubmed
    ..The contrasting effects of these two cholinoceptor agonists strongly implies that the Ca2+ entry after muscarinic receptor activation is not primarily due to activation of voltage-dependent calcium channels...
  40. Shen W, Tian X, Day M, Ulrich S, Tkatch T, Nathanson N, et al. Cholinergic modulation of Kir2 channels selectively elevates dendritic excitability in striatopallidal neurons. Nat Neurosci. 2007;10:1458-66 pubmed
    ..This cell type-specific enhancement of dendritic excitability is an essential trigger for synaptic pruning after dopamine depletion, as pruning was prevented by genetic deletion of M1 muscarinic receptors...
  41. Inoue M, Fujishiro N, Imanaga I. Hypoxia and cyanide induce depolarization and catecholamine release in dispersed guinea-pig chromaffin cells. J Physiol. 1998;507 ( Pt 3):807-18 pubmed
    ..2. Exposure to hypoxia, cyanide (CN), or muscarine facilitated CA secretion from dissociated chromaffin cells...
  42. Zaidi Z, Matthews M. Stimulant-induced exocytosis from neuronal somata, dendrites, and newly formed synaptic nerve terminals in chronically decentralized sympathetic ganglia of the rat. J Comp Neurol. 1999;415:121-43 pubmed
    ..Responses to muscarine were significantly less in denervated than in contralateral ganglia, indicating inhibition in dendrites...
  43. Olson P, Tkatch T, Hernandez Lopez S, Ulrich S, Ilijic E, Mugnaini E, et al. G-protein-coupled receptor modulation of striatal CaV1.3 L-type Ca2+ channels is dependent on a Shank-binding domain. J Neurosci. 2005;25:1050-62 pubmed
    ..Together, these results suggest that Shank promotes the assembly of a signaling complex at corticostriatal synapses that enables key GPCRs to regulate L-type Ca2+ channels and the integration of glutamatergic synaptic events...
  44. Chatonnet F, Boudinot E, Chatonnet A, Taysse L, Daulon S, Champagnat J, et al. Respiratory survival mechanisms in acetylcholinesterase knockout mouse. Eur J Neurosci. 2003;18:1419-27 pubmed
    ..In vitro, the cholinergic agonists muscarine (50-100 microm) and nicotine (0...
  45. Oldford E, Castro Alamancos M. Input-specific effects of acetylcholine on sensory and intracortical evoked responses in the "barrel cortex" in vivo. Neuroscience. 2003;117:769-78 pubmed
    ..The results revealed that Ach selectively enhances the sensory response relative to the intracortical response. Thus, pathways in the barrel cortex are differentially regulated by cholinergic inputs...
  46. Shalinsky M, Magistretti J, Ma L, Alonso A. Muscarinic activation of a cation current and associated current noise in entorhinal-cortex layer-II neurons. J Neurophysiol. 2002;88:1197-211 pubmed
    ..We suggest that the membrane current fluctuations brought about by I(CCh) channel noise may facilitate the "theta" oscillatory dynamics of these neurons and enhance firing reliability and synchronization...
  47. Ogasawara M, Shimoda N, Sato K, Kato T, Sugaya K. [The effects of the antagonists of muscarinic acetylcholine receptor subtypes in rat brain on urinary bladder contraction]. Nihon Hinyokika Gakkai Zasshi. 2002;93:427-34 pubmed
    ..We investigated the diversity of effect of each subtype in rat brain...
  48. Matsumoto M, Watanabe T, Miyagawa I. Effects of long-term estradiol treatment on the contractile response to muscarine and muscarinic receptor subtypes in the bladder of aged female rats. Biomed Res. 2007;28:309-14 pubmed
    In this study, we tried to elucidate the effect of estrogen treatment on the detrusor contractile response to muscarine and muscarine receptor subtypes of the bladder in 13-month-old female Wistar rats...
  49. Xu C, Wu M, Morozova E, Alreja M. Muscarine activates the sodium-calcium exchanger via M receptors in basal forebrain neurons. Eur J Neurosci. 2006;24:2309-13 pubmed
    ..In the present study, we examined the ionic mechanism(s) underlying the excitatory actions of muscarine in these neurons...
  50. Noble E, Bommer M, Liebisch D, Herz A. H1-histaminergic activation of catecholamine release by chromaffin cells. Biochem Pharmacol. 1988;37:221-8 pubmed
    ..These studies suggest that histamine as well as certain other neuroactive substances could play an important role in the physiology and biochemistry of adrenal medullary chromaffin cells...
  51. Inoue M, Fujishiro N, Imanaga I. Na+ pump inhibition and non-selective cation channel activation by cyanide and anoxia in guinea-pig chromaffin cells. J Physiol. 1999;519 Pt 2:385-96 pubmed
    ..2. Bath application of Ba2+ induced a dose-dependent inhibition of a muscarine-induced current (IMUS) and part of the CN-induced current (ICN) with an IC50 (concentration responsible for 50 % ..
  52. Rotiroti D, Ciriaco E, Ammendola D, Germana G, Naccari F, Germana G. Ultrastructural changes of crop-sac and lactotrophs after systemic or intraventricular administration of drugs enhancing cholinergic transmission in pigeons. Anat Anz. 1991;173:199-208 pubmed
    ..The systemic or intraventricular administration of physostigmine, carbachol and muscarine produced maximal crop-sac stimulation with milk-like secretion, as demonstrated by the observation of ..
  53. Mäthger L, Collins T, Lima P. The role of muscarinic receptors and intracellular Ca2+ in the spectral reflectivity changes of squid iridophores. J Exp Biol. 2004;207:1759-69 pubmed
    ..also be brought about by superfusing whole skin preparations with acetylcholine (ACh) (20 micro mol l(-1)) and muscarine (30 micro mol l(-1)) but not nicotine (up to 50 mmol l(-1)), suggesting that cholinergic muscarinic receptors ..