ライフサイエンスコーパス: M2 receptor

1 his type of motoneuron by acting through the m2 receptor.

2 y 4d completely antagonized carbachol at the M2 receptor.

3 erase-labeled striatal neurons expressed the m2 receptor.

4 by docking to bind to the M3 and but not the M2 receptor.

5 ion was found at the aligning residue in the M2 receptor.

6 e case of partial agonist ARC binding to the M2 receptor.

7 tion and the route of apical delivery of the M2 receptor.

8 es are identified for the IXO- and ARC-bound M2 receptor.

9 ot necessary for the apical targeting of the M2 receptor.

10 )H]N-methylscopolamine ([(3)H]NMS) to cloned M2 receptors.

11 o stimulation during prolonged activation of M2 receptors.

12 epresented only a minority (<10%) of surface m2 receptors.

13 ted processing of the V1aR and acetylcholine M2 receptors.

14 ippocampal slices, which contain presynaptic M2 receptors.

15 to M4 receptors but decreases it slightly at M2 receptors.

16 ecystokinin, were labeled with antibodies to M2 receptors.

17 pathic pain condition and the involvement of M2 receptors.

18 of Gi1alpha, prevents coupling to muscarinic M2 receptors.

19 nic agonist with apparent selectivity toward M2-receptors.

20 of the M2 muscarinic acetylcholine receptor (M2 receptor), a prototypical family A GPCR, using atomic

21 expressing FLAG-M2-GFP demonstrate that the M2 receptor achieves its apical localization after first

22 bition of peak current amplitude produced by M2 receptor activation is similar for alpha1A and alpha1

23 mic network for allosteric regulation of the M2 receptor activation.

24 ange IPSPs were presynaptically inhibited by M2 receptor activation.

25 ere studied alone or in combination with the M2 receptor agonist oxotremorine-M.

26 creased [(3)H]NMS binding in regions rich in M2 receptors and increased binding in regions rich in M1

27 reated Xenopus oocytes expressing muscarinic m2 receptors and Kir3.1/3.2a channels.

28 release major basic protein, which binds to M2 receptors and prevents binding of acetylcholine.

29 with the antagonist, N-methylscopolamine, at m2 receptors and, in the case of the strychnine analogue

30 its interactions with M3 receptors (but not M2 receptors), and this cooperativity was not evident in

31 of beta1 knockout is eliminated by specific M2 receptor antagonism.

32 of muscarine on IK(SO) was unaffected by the M2 receptor antagonist methoctramine (100 nM) but was bl

33 t 4-DAMP (100 nmol/L) but was blocked by the M2 receptor antagonist methoctramine (5 micromol/L).

34 , the M1 receptor agonist McN-A-343, and the M2 receptor antagonist methoctramine inhibited serum TNF

35 2,3-b][1,4]benzodiazepin-6-one (BIBN 99), an M2 receptor antagonist, blocked the ability of both estr

36 ng to Galphai3 antibody was inhibited by the m2 receptor antagonist, N,N'-bis[6[[(2-methoxyphenyl)met

37 t were pretreated with either the muscarinic M2-receptor antagonist, methoctramine (10(-6) M), or per

38 by direct injection of the muscarinic M1 and M2 receptor antagonists, pirenzepine and gallamine, and

39 In these compartments, m2 receptors appear to be heteroreceptors, i.e., they ar

40 nal end of the third cytoplasmic loop of the m2 receptor are required for sequestration in JEG-3 cell

41 ic acid (GABA) was used to determine whether M2 receptors are present on interneurons or thalamocorti

42 vely, but not those coupled to G(i), such as m2 receptors, are able to regulate the activity of ERK5.

43 However, m2 receptors at cholinergic synapses represented only a

44 els (Kir3.1/Kir3.2a) activated by muscarinic m2 receptors at varying levels of G protein expression w

45 oreactivity against postsynaptic muscarinic (m2) receptors at these locations.

46 beta-acetoxynortropane (5) was an agonist at M2-receptors, based on a GTP-elicited decrease in affini

47 The mean M2 receptor binding in subjects with bipolar disorder wa

48 n the levels of both M2 muscarinic mRNA, and M2 receptor binding sites in RVL compared to age-matched

49 The M2 receptor binding was compared between unmedicated sub

50 Stimulation of heterologously expressed M2 receptors, but not other Gi/Go-associated receptors (

51 responsiveness, are due to antagonism of the M2 receptor by eosinophil major basic protein.

52 ion rate of tritium-labeled THRX-160209 from M2 receptors by competing monovalent ligands that are kn

53 r, we have generated mice lacking functional M2 receptors by using targeted mutagenesis in mouse embr

54 We could recently show that the m2 receptor can efficiently interact with mutant G prote

55 LS) or deletion of Ala391 from the wild type m2 receptor completely abolished G protein coupling.

56 ansfected COS-7 cells showed that all mutant m2 receptors containing extra Ala residues C-terminal of

57 The distribution of M2 receptors correlates well with previous reports of th

58 +) current in colonic smooth muscle cells by M2 receptor coupled to Galphai-G protein and c-src activ

59 Compound 1f also exhibited low activity at m2 receptors coupled to the inhibition of adenylyl cycla

60 the N-terminus of Gi1alpha neither prevented M2 receptor coupling nor permitted M1 receptor coupling.

61 We also show that this pathway mediates M2 receptor coupling to metabotropic nonselective cation

62 d in the context of Gq(alpha) sufficient for M2 receptor coupling.

63 M2 receptor-current coupling was disrupted by inhibiton

64 ld be accounted for either by a reduction in M2 receptor density or affinity or an elevation in endog

65 tors localized to submucosal glands, whereas M2 receptors did not.

66 and some differences were found between this m2 receptor distribution pattern and previous results fo

67 Allergen-induced M2 receptor dysfunction is absolutely dependent upon an

68 this effect was markedly reduced, confirming M2 receptor dysfunction.

69 tudies with mutant mAChRs indicated that the M2 receptor epitopes involved in the binding of tacrine

70 Furthermore, these results suggest that M2 receptor expression is under the control of a cytokin

71 pment of hypertension, the altered medullary M2 receptor expression may play a role as an initiating

72 (N-acetylsphingosine) was without effect on m2 receptor expression.

73 In the heart, ETS evoked a decrease in m2-receptor expression.

74 or protein and mRNA expression and uncoupled M2 receptors from adenylyl cyclase.

75 Thus, despite apparent recovery of normal M2 receptor function after viral infection or ozone, lin

76 ine release, suggesting decreased inhibitory M2 receptor function and/or expression.

77 Neuronal M2 receptor function can be studied using selective agon

78 ovide the first direct evidence that altered M2 receptor function contributes to mood dysregulation i

79 prevented hyperresponsiveness, and protected M2 receptor function in the antigen-challenged animals w

80 with HP1/2, but not with LAM1-116, protected M2 receptor function in the antigen-challenged animals.

81 Loss of M2 receptor function is associated with the accumulation

82 with ovalbumin and hyperresponsiveness, and M2 receptor function tested 24 h later with the muscarin

83 Likewise, loss of M2 receptor function was demonstrated since the agonist

84 ensitized and challenged with ovalbumin, and M2 receptor function was tested.

85 with virus, (which causes temporary loss of M2 receptor function), and then allowed to recover for 8

86 )-gamma on acetylcholine release, inhibitory M2 receptor function, and M2 receptor gene expression.

87 VLA-4 and L-selectin is critical for loss of M2 receptor function, guinea pigs were pretreated with m

88 subsequent formation of functionally coupled m2 receptor-G protein heterotrimers (Galpha((GDP))betaga

89 h, in contrast to the Gi/o-coupled wild type m2 receptor, gained the ability to efficiently activate

90 Different levels of specific m2 receptor-Galpha coupling were established by uncoupli

91 olation of the promoter region for the chick m2 receptor gene and defined a region of the chick m2 pr

92 nchoconstriction both by directly inhibiting M2 receptor gene expression and by causing release of IF

93 chain reaction method, we demonstrated that M2 receptor gene expression was decreased by more that a

94 causing release of IFN-gamma which inhibits M2 receptor gene expression.

95 elease, inhibitory M2 receptor function, and M2 receptor gene expression.

96 ty, and nuclear run-on assays showed reduced m2 receptor gene transcription.

97 fect is associated with increased muscarinic M2-receptor/Gi protein-coupled expression and function.

98 Concentrations that fully blocked cloned M2 receptors had no effect on M4 receptors, but slightly

99 The lack of M1 or M2 receptors had no significant effect on the magnitude

100 gs open the possibility that the loss of the m2 receptor in Alzheimer's disease may in part be due to

101 ve state crystal structure of the muscarinic M2 receptor in complex with iperoxo, we explored potenti

102 erefore, we analyzed the localization of the m2 receptor in correlation with synapses by electron mic

103 The localization of the m2 receptor in cortical neurons and the sparing of m2 im

104 of ACh release is mediated primarily by the M2 receptor in hippocampus and cerebral cortex, but pred

105 evidence for widespread localization of the m2 receptor in noncholinergic neurons and fibers of the

106 Emission tomographic study of the loss of m2 receptors in AD has been limited by the absence of av

107 ssion tomographic (PET) study of the loss of m2 receptors in AD.

108 cells and interneurons were stained for the M2 receptors in both the glomerular and extraglomerular

109 In conclusion, m2 receptors in smooth muscle couple to inhibition of ad

110 Finally, our findings suggest that most m2 receptors in the cholinergic basal forebrain are loca

111 therefore, they are not the major source of m2 receptors in the cortex.

112 milar interaction between A1 and presynaptic M2 receptors in the hippocampus.

113 Furthermore, pharmacological activation of M2 receptors in the pIC using oxotremorine completely re

114 increase in the number of binding sites for M2 receptors in the RVL.

115 ,000 ng) was without effect, suggesting that M2 receptors in this brain region do not play a signific

116 d for distinguishing the functional roles of M2 receptors in tissues containing several muscarinic re

117 Interestingly, however, three mutant m2 receptors in which different segments of the second a

118 amine the distribution of muscarinic type 2 (M2) receptors in the visual thalamus of the cat.

119 and more specifically the type 2 muscarinic (M2) receptor, in the pathogenesis of depressive symptoms

120 ed to recover for 8 wk (to allow recovery of M2 receptors), indomethacin prevented both gallamine's p

121 ion of the beta3 subunit, the sensitivity to M2 receptor-induced G-protein inhibition was reduced for

122 ilar to the changes it produces in relief of M2 receptor-induced inhibition.

123 a6-loop of Gi1alpha are involved in 5-HT and M2 receptor interactions.

124 The M2 receptor is an inhibitory prejunctional autoreceptor.

125 Here, activation of the M2 receptor is directly observed via accelerated molecul

126 Previous studies have shown that the M2 receptor is localized at steady state to the apical d

127 intracellular carboxyl-terminal tail of the m2 receptor is neither sufficient nor required for the m

128 ivity in lesioned monkeys indicates that the m2 receptor is synthesized largely within the cortex and

129 The muscarinic m2 receptor is the major acetylcholine receptor subtype

130 mulation and a high density of acetylcholine M2 receptors is in accord with this as are tests of vent

131 RGS4(C2V) are necessary for association with m2 receptor-Kir3.1/Kir3.2a channel complexes, where the

132 for agonist-induced internalization for the m2 receptor lies in the carboxyl-terminal fifth of the r

133 ic receptor subtypes present in the VTA, the M2 receptor (M2R) is most implicated in autoregulation a

134 Muscarinic m2 receptors (M2Rs) are implicated in autoregulatory con

135 ing asymmetric synapses, indicating that the m2 receptor may modulate excitatory neurotransmission at

136 w external potassium eliminated the enhanced M2-receptor mediated contraction.

137 strated enhanced adenosine A1 and muscarinic M2 receptor-mediated bradycardic responses.

138 ibed to a defect in BK channel opposition of M2 receptor-mediated contractions.

139 f BK/beta1 channels is to oppose cholinergic M2 receptor-mediated depolarization and activation of ca

140 shed the mutation-induced enhancement of the M2 receptor-mediated response but had a minimal effect o

141 sis showed a small and transient increase in m2-receptor mRNA levels up to 2 hr but no long term (24

142 Muscarinic M2 receptors, nitric oxide and vasoactive intestinal pep

143 re, together with that of the G(i/o)-coupled M2 receptor, offers possibilities for the design of mACh

144 ifference of LV protein levels of muscarinic M2 receptors or G protein Galpha(i1,2), Galpha(i3), and

145 s evoked by agonist activation of muscarinic m2 receptors or serotonin 1A receptors were dramatically

146 The results favor oligomers of the M2 receptor over monomers as the biologically relevant s

147 Our data suggest that M2 receptors play an important role both in blocking tha

148 he ACC pathway to DLPFC (area 32 to area 9), m2 receptors predominated in ACC axon terminals and in m

149 DLPFC area 46 to DLPFC area 9, postsynaptic m2 receptors predominated in targeted spines of presumed

150 cytokines markedly down-regulated muscarinic M2 receptor protein and mRNA expression and uncoupled M2

151 cellular and subcellular distribution of the m2 receptor protein and mRNA were examined in normal mon

152 The m2 receptor protein is enriched both in layer IV axons o

153 Immunocytochemistry revealed that the m2 receptor protein is expressed primarily in noncholine

154 ), we speculated that agonist binding to the m2 receptor protein results in conformational changes th

155 The remarkable segregation of the m1 and m2 receptor proteins to projection and local circuit neu

156 6-tetrahydro-1-me thylpyridine), a selective M2 receptor radioligand.

157 The disulfide cysteine mutations in M2 receptors reduced the allosteric potencies of the tes

158 c afferents onto projection neurons, whereas m2 receptors regulate acetylcholine release from axons o

159 t the presence of three of the four targeted m2 receptor residues (Val385, Thr386, and Ile389) is ess

160 ts for this interaction to occur, these four m2 receptor residues were replaced, either individually

161 ]pirenzepine or [3H]AFDX 384 to label M1 and M2 receptors, respectively.

162 o activate both G(q/11) and G(i3) via m3 and m2 receptors, respectively.

163 However, selective agonist occupancy of the M2 receptor resulted in enhanced M2-M2 homomer interacti

164 Thus, the reduced levels of the m2 receptor seen in AD cortex probably reflect changes i

165 In the nicotine-exposed group, m2-receptors showed a significant reduction that persist

166 We also report the structure of the M2 receptor simultaneously bound to the orthosteric agon

167 -160209 binds in a multivalent manner to the M2 receptor, simultaneously occupying the orthosteric si

168 oride current is activated in the absence of M2 receptor stimulation by the injection of PIP3, and PI

169 t affinity of the multivalent ligand for the M2 receptor subtype (apparent pK(I) = 9.51 +/- 0.22) tha

170 ligands exhibit greatest affinity toward the M2 receptor subtype and lowest affinity toward M5.

171 6.0), 2) specificity of THRX-160209 for the M2 receptor subtype compared with the closely related M4

172 The entire DLG stained darkly for the m2 receptor subtype, except for patchy label in the medi

173 ransferase activity, or in muscarinic M1 and M2 receptor subtypes in autism.

174 c receptors, and it appears that it is these M2 receptors that are dysfunctional in animal models of

175 The results suggest that m2 receptors that are located both pre- and postsynaptic

176 ggest that ACh enhances Cav1.2b currents via M2 receptors that couple sequentially to Gbetagamma, PI3

177 ng, were equivalent to (AC) or greater than (m2-receptors) those seen with prenatal ETS mimicking act

178 Since exposure to ozone also caused neuronal M2 receptors to become dependent upon cyclooxygenase the

179 ic (i.e. dualsteric) agonists for muscarinic M2 receptors to demonstrate the existence and function o

180 The ability of the resulting mutant m2 receptors to interact with a mutant alpha(q) subunit

181 We show that the stimulatory pathway linking M2 receptors to these chloride channels consists of Gbet

182 These results suggest that the m1 and m2 receptors use distinct cellular mechanisms or pathway

183 Targeting these cortical muscarinic M2 receptors using central cholinomimetics could be an e

184 hic pain, and suggest that targeting insular M2 receptors using central cholinomimetics could be used

185 quantitatively analyzed the distribution of M2 receptors using electron microscopy.

186 munohistochemistry for muscarinic subtype 2 (m2) receptors using a monoclonal subtype-specific antibo

187 tification of a four-amino-acid motif on the m2 receptor (Val385, Thr386, Ile389, and Leu390) that is

188 for this interaction to occur, the wild type m2 receptor was co-expressed with a series of mutant alp

189 neurons of normal and lesioned monkeys, the m2 receptor was located peri- and extra-synaptically, su

190 Procaterol-induced down-regulation of M2 receptors was fully blocked by N-[2-(methylamino)ethy

191 Using molecular modelling of the M2 receptor we found that E172 and E175 in the second ex

192 The m2 receptors were also enriched at glutamatergic synapse

193 holine release increased when the inhibitory M2 receptors were blocked using atropine (10(-)5 M) and

194 The m2 receptors were concentrated at cholinergic synapses l

195 In all nuclei, m2 receptors were localized at the membrane of motoneuro

196 rtion (20-30%) of plasma membrane-associated m2 receptors were located at glutamatergic synapses.

197 Conversely, in muscle cells where only m2 receptors were preserved, ACh caused an accentuated d

198 line binding to G protein-coupled muscarinic M2 receptors, which activate heterotrimeric G(i/o) prote

199 trategic synaptic localization of muscarinic m2 receptors, which inhibit neurotransmitter release pre

200 ne transporter and especially the muscarinic M2 receptors, which was confirmed by Western blot analys

201 Remarkably, the wild type m2 receptor, while unable to efficiently stimulate wild

202 ing of [(3)H]NMS and [(3)H]oxotremorine-M to M2 receptors with Hill coefficients near 1, and blocked

203 ed orbitofrontal and mid-temporal muscarinic M2 receptors with psychosis and hallucinations.

204 particular, we examined the distribution of M2 receptors with respect to the known sites of PBR term

205 the VTIL motif in such constitutively active m2 receptors with the corresponding m3 muscarinic recept