muscarinic receptors

..The results indicate that leukocytes are not a suitable model to investigate the muscarinic receptor function in relation to bronchial asthma...

..These results suggest that M2/4 muscarinic receptors in the mesopontine tonically influence SNc basal dopamine cell activity and striatal dopamine release.

..These novel results implicate nucleus accumbens muscarinic receptors in the modulation of appetitive learning, performance, and motivation for food.

..Simultaneous recordings from pyramidal cell pairs reveal synchronous theta-frequency IPSPs in neighboring pyramidal cells, suggesting that these IPSPs may help entrain or modulate small groups of pyramidal cells...

..CONCLUSIONS: The results obtained show that muscarinic receptors may be involved in airway inflammation in COPD subjects through ACh-induced, ERK1/2-dependent LTB4 release...

..were antagonized either by scopolamine (3 microM) or by pirenzepine (10-100 nM), an antagonist of M1-like muscarinic receptors, but not by methoctramine (300 nM), an antagonist of M2-like muscarinic receptor...

..How DA signaling is regulated by striatal muscarinic receptors (mAChRs) is unresolved; contradictory reports indicate suppression or facilitation, implicating several ..

..receptor antagonists scopolamine and pirenzepine fully prevented the induction of LTP suggesting that the activation of M1-like muscarinic receptors is a crucial event in the conditioning phase of this form of synaptic plasticity.

..contraction of the urinary bladder, which is required for voiding, is predominantly mediated by muscarinic receptors, primarily the M3 subtype, with the M2 subtype providing a secondary backup role...

..Moreover, a disturbed regulation of sphingolipid metabolism in the vascular wall may therefore play a role in the aetiology/pathology of disease states characterized by endothelial dysfunction...

..Antibody capture GTPgamma35S binding using scintillation proximity assay technology provides a convenient, productive alternative to immunoprecipitation for exploration of receptor-G protein interaction in cells and tissues...

..We have investigated the role of M2-like muscarinic receptors in striatal LTP by utilizing intracellular recordings in vitro from a rat corticostriatal slice preparation...

..0 s) to become nearly contemporaneous with Galpha(q)/PLC interaction. Evidently, channel release of PIP(2) and closure are rapid, and the availability of active PLC limits the rate of M current suppression...

b>Muscarinic receptors activate Ras through a pathway distinct from that mediated through translocation of the exchange factor mSos1 by receptor tyrosine kinases...

..RESULTS: All 5 muscarinic receptors were detected in fresh human bladder tissue by reverse transcriptase-polymerase chain reaction RNA...

..We found that stimulation of muscarinic receptors, either by an agonist or by the synaptic release of acetylcholine, led to long-term depression (LTD) of ..

b>Muscarinic receptors play key roles in the control of gastrointestinal smooth muscle activity. However, specific physiological functions of each subtype remain to be determined...

Mamba venoms contain peptides with high selectivity for muscarinic receptors. Due to the limited availability of the M(1) muscarinic receptor-selective MT7 or m1-toxin 1, the peptide was expressed in Sf9 cells using a synthetic cDNA and ..

..enzymatic activities are known to be modulated by dopamine D(1), beta-noradrenergic, 5HT1A and cholinergic muscarinic receptors. Here we study the effect on retrieval of this task of well-known agonists and antagonists of these ..

..An important implication of this analysis is that extremely weak partial agonists (which may in practice be indistinguishable from antagonists) may produce significant receptor internalization...

..1, 3, 24, and 73%) as P(O) increased 525-fold in three stages...

..on mechanical hypersensitivity involves activation of spinal alpha(2)-adrenergic receptors followed by muscarinic receptors (most likely M(1)) and the NO cascade...

..activate dopamine neurons of the substantia nigra and ventral tegmental area (VTA) via nicotinic and muscarinic receptors. The nicotinic receptors near the VTA have been proposed to be important for nicotine self-administration ..

..However, until recently, the link between the receptors and the channels has remained elusive. Here, we summarize recent developments that have begun to clarify this link and discuss their implications for physiology and medicine...

..that endogenous ACh in the spinal cord acts as a transmitter anti-nociception, and that ACh release regulated by presynaptic M(3) muscarinic receptors in the spinal cord is involved in the second phase of nociception induced by formalin.

..Together these results indicate that M(2) receptors are coupled to Src tyrosine kinase and subsequent activation of ERK in cultured CSMC...

..Co-expression of Ras-GRF1 with subtype 1 human muscarinic receptors in COS-7 cells allowed mapping of a carbachol-stimulated phosphorylation site to a region composed of ..

..the binding of the chiral forms of ketamine to opioid (mu, delta and kappa), phencyclidine, sigma and muscarinic receptors and we have performed detailed concentration-response experiments in the guinea-pig ileum preparation...

..We tested the hypothesis that the pro-inflammatory cytokine profile in IBS is driven by the cholinergic system and determined if the responses are mediated by muscarinic receptors.

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Emerging evidence indicates that muscarinic receptors and ligands play key roles in regulating cellular proliferation and cancer progression...

b>Muscarinic receptors have been implicated in the regulation of cognition and psychosis based on pharmacological evidence from pre-clinical and clinical studies...

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..New compounds are now being developed that have the potential to selectively target individual muscarinic receptors in the central nervous system...

Airway smooth muscle is richly endowed with muscarinic receptors of the M(2) and M(3) subtype...

We have previously suggested that presynaptic M(2)-muscarinic receptors (M(2)R) are involved in the control of the time course of evoked acetylcholine release in the frog neuromuscular junction...

..15 +/- 0.23 and 9.63 +/- 0.28, respectively. These results suggest that the muscarinic M3 receptor subtype mediates both endothelium-dependent relaxation and contraction to acetylcholine in SHR aorta...

..The alterations of mAChRs in AChE -/- mice suggest that mAChR downregulation may contribute to the limited efficacy of AChE inhibitors in Alzheimer's disease treatment...

..These results show that the muscarinic regulation of GABA transmission is impaired in the AD model, probably due to the Abeta-mediated interference of mAChR activation of PKC...

..This has been found previously to be due to activation of muscarinic receptors of the M1 subtype, probably located on sympathetic nerve terminals...

b>Muscarinic receptors were solubilized from porcine atria in digitonin-cholate and were purified by chromatography on DEAE-Sepharose and 3-(2'-aminobenzhydryloxy)tropane-Sepharose...

Leukocytes contain both nicotinic and muscarinic receptors, and while activation of nicotinic receptors suppresses immune/inflammatory responses, the role of muscarinic receptors in immunity is unclear...

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..The novel insights gained from these studies should prove instrumental for the development of novel classes of muscarinic drugs...

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To study a potential role for muscarinic receptors in the inhibition of deprivation-induced excessive axial elongation and myopia in a monkey model.

..Taken together our results indicate that muscarinic activity controls the survival of retinal ganglion cells through a mechanism involving the release of polypeptides and activation of Irk receptors...

..RESULTS: Western blot demonstrated PGP 9.5, M(1), M(2), and M(3) muscarinic receptors and alpha(1A)-, beta(1)-, beta(2)-, and beta(3)-adrenergic receptors in mouse conjunctiva...

1. Release of acetylcholine from parasympathetic nerves is inhibited by neuronal M(2) muscarinic receptors. The effects of streptozotocin-induced diabetes on prejunctional M(2) and postjunctional M(3) muscarinic receptor function in rat ..

..In the present study, we compared modulation of CaV2.3 by the three Galphaq/11-coupled muscarinic receptors (M1, M3, and M5). Our data indicate that these receptors trigger comparable stimulation of CaV2.3...

..The findings suggest that sorbitol plays a role in the pathogenesis of diabetic cystopathy in rats rendered diabetic by streptozotocin. Aldose reductase inhibitors may be useful in the treatment and prevention of diabetic cystopathy...

..QNB), particularly [123I]-(R,R)-I-QNB, are currently being assessed as in vivo ligands to monitor muscarinic receptors in Alzheimer's disease (AD) and dementia with Lewy bodies (DLB), relating changes to disease symptoms and ..

..Oxo-M stimulated IL-2 receptor mRNA expression and DNA synthesis. Our results suggest that muscarinic receptors, perhaps M(1) receptors are involved in the enhancement of TCR-induced IL-2 production and IL-2 receptor ..

..Elimination of the described effects of Ach by atropine, the antagonist of muscarinic receptors, and identification of the type 3 muscarinic receptors (m3) in isolated hepatocytes as well as in whole ..

..The present study was carried out with wild-type and chimeric muscarinic receptors to determine whether UH-AH 37 might also have an allosteric mode of action...

..Collectively, these data show that in the absence of a high affinity M5 selective antagonist, affinity data for a large range of antagonists is critical to define operationally the M5 receptor subtype...

Parasympathetic nerve stimulation causes slowing of the heart rate by activation of muscarinic receptors and the subsequent opening of muscarinic K+ channels in the sinoatrial node and atrium...

..diphenylacetate (4-DAMP) was synthesized, and its conversion to an aziridinium ion and interaction with muscarinic receptors was investigated. When dissolved in aqueous solution at pH 7...

..The present data suggest that local ACh, acting through mAChRs, regulates the cortical dynamics making cortical circuits respond to specific stimuli...

..Our results indicate that different mAChR subtypes regulate different forms of long-term synaptic plasticity in the mouse visual cortex, activating specific G proteins and downstream intracellular mechanisms...

..Astrocytes express muscarinic receptors whose activation stimulates a robust intracellular signaling, although the role of these receptors in glial ..

..We conclude that previously reported differences relate to the use of inhibitors rather than experimental protocols and that the overall data do not support a role for PLC in M(3) muscarinic receptor-mediated rat bladder contraction...

..5 microg/1 microl) produced opposite response. On the basis of the above findings, we can deduce that ACh and mAChRs are involved in the modulation of nociceptive information transmission in the hippocampal CA1...

..Therefore, imidafenacin will have higher affinities for M3 and M1 receptors and higher selectivity for the urinary bladder than for the salivary gland...

..These results suggest that 6beta-acetoxy nortropane could exert a beneficial effect on the progress of Alzheimer's disease by promoting amyloid precursor protein processing through alpha-secretase...

..Changes were not detected for relaxation by adrenergic agonists. In conclusion, aging caused a decrease of MCh potency, which is probably related to the reduction of calcium sensitivity in jejunum...

..the presence of these receptors in the motor endplates and conclude that M1-, M2-, M3- and M4-type muscarinic receptors are present in all the neuromuscular junctions of the rat muscle both in newborn and adult animals...

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..We conclude that acetylcholine acting via muscarinic receptors is the key neurotransmitter in the mechanism underlying the natural activation of the locust flight CPG...

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..of the ventral subiculum by carbachol increases dopamine efflux in the nucleus accumbens by stimulation of muscarinic receptors, and that the ventral subiculum-nucleus accumbens projection system is sensitive to muscarinic M(2)/M(4) ..

..We show that the way in which M1 and M2 muscarinic receptors modulate neurotransmission can differ between the developing and adult rat neuromuscular synapse.

..Therefore, PB, acting via m3 receptors, can effectively counteract effects arising from the interactions of soman with m2 receptors in the brain...

..Our results suggest that PKC activation leads to a decrease in retinal cells proliferation through the release of acetylcholine and brain derived neurotrophic factor in the culture, and activation of M1 and TrkB receptors, respectively...

..These data demonstrate subtype-specific regulation of the expression and function of muscarinic receptors in the retina.

..work from our laboratory indicates that bile acids, specifically lithocholic acid conjugates, interact with muscarinic receptors on gastric chief cells...

..We conclude that, while the nicotinic inputs to the PPN may help modulate the developmental decrease in REM sleep, the muscarinic inputs appear to modulate different types of cells differentially...

..Such dual complementary actions allow ACh and nicotine to enhance wakefulness by inhibiting sleep-promoting systems while facilitating other wake-promoting systems...

..The M(3) and M(2)/M(4) subtypes on a subpopulation of interneurons are important for regulation of glutamate release from interneurons in the spinal dorsal horn...

..These results indicate that Z-338 is a potent antagonist not for muscarinic M3 receptor but for both muscarinic M1 and M2 receptors. Thus, Z-338 is a gastrokinetic agent with a unique profile...

..The results suggest that acetylcholine has mixed effects at the HMN with muscarinic-mediated GG suppression masking nicotinic excitation...

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..OXO and Cch suggested that OXO is able to detect differences in the response of structures enriched in M(4) muscarinic receptors, showing a lower potency to stimulate these brain areas...

..In vitro isolated organ experiments correlated well with the receptor binding results, and in vivo investigations indicated the soft character of the compounds...

..It follows that the mechanisms regulating the amount and the time course of transmitter release are different and that, among other factors, they are altered by presynaptic nicotinic receptors...

..Acetylcholine receptors are of two main types, nicotinic and muscarinic. Muscarinic receptors are in the G-protein coupled receptor superfamily, and five different muscarinic receptors have been ..

..The results also suggest that both transcriptional and post-transcriptional mechanisms may potentially need to be regulated to induce TH protein in response to some stimuli...

..Stimulation of septal muscarinic receptors by carbachol also increased hippocampal ACh release...

..The current study suggests that synaptic release of ACh results in a complex and differential mAChR-mediated modulation of cellular excitability within the hippocampal interneuron population...

..In conclusion, these results provide evidence for the presence of M(2)- and M(3)-mAChR, at the mRNA and protein level, in the rat myometrium and indicate that estrogen induces an increase in myometrial responsiveness to mAChR agonists...

..4 These results may contribute to a better understanding of the modulatory role of the parasympathetic muscarinic system on normal human fibroblast function...

..The overactivity is associated with an enhanced sensitivity to carbachol, which is partly explained by an increase in receptor density, but there appears to be no change in receptor/G-protein coupling...

..The isolated mouse whole bladder has proved a viable, robust model in which to demonstrate the pharmacological characteristic of the bladder and adds to the repertoire of in vitro tools for investigating potential therapeutic agents...

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..To investigate the potential of antimuscarinic agents for sensory mechanisms in overactive bladder using intravesical instillation...

M(3) muscarinic receptors mediate cholinergic-induced contraction in most smooth muscles...

..The hypothesis is proposed that muscarinic receptors may be involved in the (presumably Ca(2+)-dependent) modulation of the nuclear status during the first cell ..

..27+/-0.09 (spirotramine) and 8.51+/-0.02 (AM170). Competition radioligand binding studies, using native muscarinic receptors from rat tissues (M(1), cortex; M(2), heart; M(3), submaxillary gland) or from NG 108-15 cells (M(4)) and ..

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..Locally impaired cardiac acetylcholine release may therefore represent a pathophysiological link to sudden cardiac death in elderly and diabetic patients...

..Compound 14a showed high selectivity for M(3) receptors over the other muscarinic receptor subtypes (M(1)/M(3) = 380-fold, M(2)/M(3) = 98-fold, M(4)/M(3) = 45-fold, M(5)/M(3) = 120-fold)...

..present line of investigation was initiated by our unanticipated observation that bile acids interact with muscarinic receptors. M3 muscarinic receptors (M3R), which are over-expressed in most colon cancers, are key players in colon ..

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..Given the importance of mucins in protection of the oral cavity and the primary role of muscarinic receptors in eliciting mucous cell secretion, studies are proposed to determine the regulation by agonist of ..

..We will measure the effect of acetylcholine agonists specific for nicotinic or muscarinic receptors on myogenic activity (hypothesis 4)...

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..be tested in this proposal is that bile acids induce colon cancer cell proliferation by interaction with M3 muscarinic receptors (M3R), thereby causing transactivation of epidermal growth factor receptors (EGFR)...

..present line of investigation was initiated by our unanticipated observation that bile acids interact with muscarinic receptors. M3 muscarinic receptors (M3R), which are over-expressed in most colon cancers, are key players in colon ..

..During intubation of the trachea, parasympathetic nerves release acetylcholine that act on M3 muscarinic receptors on airway smooth muscle to promote bronchoconstriction...

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..In particular, Gq/11-linked receptors such as the type 1 metabotropic glutamate and M1, M3, and M5 muscarinic receptors, activate these currents by altering plasma membrane PIP2 and increasing intracellular Ca2+ concentrations...

..Rational therapy of a number of pathophysiological conditions, e.g. Alzheimer's disease, can ultimately benefit from this knowledge...

..A family of GPCRs that mediates the action of acetylcholine includes five members called muscarinic receptors (M1R-M5R)...

..but stimulates acetylcholine release from cholinergic neurons that innervate the islets thereby activating muscarinic receptors on the pancreatic -cell...

..Accordingly, knowledge of the signal transduction pathways that regulate VSOAC is an essential prerequisite for the rational design of therapeutic agents. ..

..Novel morphological data should be obtained for AD and PD, and these data should provide a good basis for physiological work with the toxin, and for understanding which cells are most likely to be controllable with muscarinic ligands...

..The results from the proposed studies will identify future studies on ways to prevent the motor dysfunction that occurs with gallbladder inflammation. ..

..Activation of muscarinic receptors in mouse neuroblastoma cells results in Ca2+ release and cyclic GMP formation; with the latter response ..