ライフサイエンスコーパス: alpha7 nAChR

1 alpha7 nAChR is also present in lymphocytes, dendritic c

2 alpha7 nAChR mRNA is detected by RT-PCR and cell surface

3 alpha7 nAChR, CFTR, and adenylyl cyclase-1 are physicall

4 alpha7 nAChRs are expressed widely throughout the brain,

5 alpha7 nAChRs at the TSC may act as a sensor for spillov

6 alpha7-nAChRs are downstream of IL-13 but upstream of GA

7 quin oline-8-sulfonamide (4BP-TQS) activate alpha7 nAChRs more slowly and cause only low levels of a

8 hese novel findings indicate that activating alpha7 nAChR is a promising treatment for cognitive impa

9 d function of the nicotinic receptor alpha7 (alpha7-nAChR).

10 a7 nAChRs and is recapitulated by GTS-21, an alpha7 nAChR partial agonist.

11 ne and NS1738 was mimicked by PNU-282987 (an alpha7 nAChR agonist), and was absent in alpha7 nAChR kn

12 However, an alpha7 nAChR antagonist had no effect at any age.

13 that nicotine in combination with NS1738, an alpha7 nAChR-positive allosteric modulator, strongly pot

14 Maximal transient probability of an alpha7 nAChR being open with rapid agonist applications

15 tential of (18)F-ASEM ((18)F-JHU82132) as an alpha7-nAChR radioligand for PET.

16 SSR180711, an alpha7-nAChR-selective partial agonist, blocked (18)F-AS

17 Pharmacological inhibition using an alpha7-nAChR antagonist or genetic deletion of nAChR alp

18 00-fold selectivity over the alpha3beta2 and alpha7 nAChR subtypes.

19 ts mediated by alpha3beta4, alpha3beta2, and alpha7 nAChR subtypes.

20 he other major subtypes, the alpha4beta2 and alpha7 nAChR.

21 ditory gating deficits in schizophrenia, and alpha7 nAChR agonists can potentially reverse these defi

22 nding site, we find that the alpha4beta4 and alpha7 nAChRs employ different agonist-receptor binding

23 d both beta2 subunit-containing (beta2*) and alpha7 nAChRs in the effects of nicotine in models of an

24 >1 microM, also inhibits these receptors and alpha7 nAChRs.

25 -component combination of PMCA2, PSD-95, and alpha7-nAChR offers a novel mechanism for tight control

26 In vivo cerebral binding of (18)F-ASEM and alpha7-nAChR expression in mutant DISC1 mice, a rodent m

27 ncreased the levels of alpha7-nAChR mRNA and alpha7-nAChR transcription in human SCC-L cell lines and

28 l prefrontal cortex and substantia nigra and alpha7-nAChR binding in the lateral and ventromedial hyp

29 pha7 subunit protein on the cell surface and alpha7-nAChR function, but not alpha7 subunit mRNA, sugg

30 mucus formation is independent of IL-13, and alpha7-nAChRs are critical in airway mucous cell metapla

31 Acetylcholine and alpha7-nAChRs might serve as therapeutic targets to cont

32 subtypes present on CG neurons (alpha3*- and alpha7-nAChRs) and lowered the frequency and amplitude o

33 beta2-nAChR relative to the alpha3beta4- and alpha7-nAChRs than 5a and 5g.

34 for alpha4beta2-nAChR over alpha3beta4- and alpha7-nAChRs.

35 tagonists at alpha4beta2-, alpha3beta4-, and alpha7-nAChRs.

36 ere evident, with most compounds emerging as alpha7 nAChR agonists and alpha4beta2 nAChR antagonists.

37 trafficking of alpha7 subunits and assembled alpha7-nAChRs to the cell surface.

38 ine receptors (nAChRs) and a full agonist at alpha7 nAChRs.

39 Because alpha7-nAChRs have a high permeability to Ca(2+), we per

40 r intracellular calcium signaling but not by alpha7 nAChR antagonists.

41 Hence, LTP was prevented by alpha7 nAChR antagonists dihydro-beta-erythroidine and m

42 TFTs, is essential for their recognition by alpha7 nAChR, although it is less important for interact

43 c neurotransmission in the brain mediated by alpha7 nAChRs and that this has a profound effect on reg

44 2* nAChRs, whereas ACh responses mediated by alpha7 nAChRs were not hampered.

45 fibers elicits synaptic currents mediated by alpha7 nAChRs.

46 egulation of signal transduction pathways by alpha7 nAChRs in cells such as those that regulate infla

47 -surface expression and calcium signaling by alpha7 nAChRs.

48 f endogenous PPARalpha ligands, triggered by alpha7-nAChR activation, blocks in rats nicotine-induced

49 at the binding of (18)F-ASEM was mediated by alpha7-nAChRs and the radioligand was suitable for drug

50 In contrast, STN neurons containing alpha7 nAChRs (alpha7 neurons) received more GABAergic i

51 need for the technical capability to control alpha7 nAChR gene expression.

52 deletions and duplications lead to decreased alpha7 nAChR-associated calcium flux.

53 excision is an effective approach to delete alpha7 nAChR expression in a cell-specific manner.

54 nd orthosteric agonists results in different alpha7 nAChRs open-channel conformations.

55 tive recruiters and activators of endogenous alpha7 nAChR-dependent cholinergic pathways to reduce br

56 rove cognition in schizophrenia by enhancing alpha7 nAChR function may require consideration of these

57 Here we explore alpha7-nAChR localization and actions in primate dlPFC a

58 e here show that human NK cells also express alpha7 nAChR.

59 nsitization kinetics of native and expressed alpha7 nAChRs.

60 ponse to acetylcholine in oocytes expressing alpha7 nAChRs with an IC50 of 3.24 +/- 0.7 muM.

61 d neuroadaptations; conversely, facilitating alpha7 nAChRs activation specifically in the VTA promote

62 EPSC decay time and prolonged both the fast (alpha7-nAChR-mediated) and slow (alpha3*-nAChR-mediated)

63 Finally, alpha7-nAChR was expressed at significantly higher level

64 7(LBDEx4007Ehs)) which we refer to as floxed alpha7 nAChR conditional knockout or alpha7nAChR(flox).

65 vity, the highest-potency building block for alpha7 nAChRs, i.e., 3alpha-azido-N-methylammonium tropa

66 -beta-erythroidine that was not observed for alpha7 nAChRs at comparable concentrations.

67 nes and aromatic groups were most potent for alpha7 nAChRs.

68 were generally ~2-fold lower than those for alpha7 nAChRs.

69 y for alpha4beta2-nAChR and low affinity for alpha7-nAChR.

70 the currently available PET radioligands for alpha7-nAChR are suitable for quantitative PET imaging,

71 ylcholine might be the biological ligand for alpha7-nAChRs to trigger airway mucus formation.

72 pposed to being incorporated into functional alpha7 nAChRs at the cell membrane.

73 inals, indicating the presence of functional alpha7 nAChRs at presynaptic terminals.

74 ost-translational upregulation of functional alpha7-nAChRs.

75 The effects on release require functional alpha7-nAChRs and may to depend on CAST/ELKS (calpastati

76 drugs demonstrated that [(18)F]7a is highly alpha7-nAChR selective.

77 aggression, and demonstrate that hippocampal alpha7 nAChR signaling is necessary and sufficient to li

78 nt existing receptor subtypes, the homomeric alpha7 nAChR has attracted considerable attention becaus

79 ncatenated (alpha7)5-nAChRs or for homomeric alpha7-nAChRs constituted from unlinked alpha7 subunits.

80 mpared pharmacological profiles of homomeric alpha7-nAChRs and alpha7beta2-nAChRs.

81 g memory; however, little is known about how alpha7-nAChRs influence dlPFC cognitive circuits.

82 of these proteins toward the homomeric human alpha7 nAChR.

83 g ligand binding to channel opening in human alpha7 nAChR.

84 in AChBP and, by extrapolation, in the human alpha7 nAChR as determined by electrophysiology measurem

85 d substantially reduced potency at the human alpha7 nAChR relative to alpha-GID, a desirable feature

86 electrophysiological recordings on the human alpha7 nAChR we demonstrate that the identified fragment

87 acellular ligand-binding domain of the human alpha7 nAChR, to investigate the structural determinants

88 0.03 mum) and with lower efficiency to human alpha7 nAChR (IC(50) 22 +/- 2 mum).

89 sitive allosteric modulators (PAMs) of human alpha7 nAChRs expressed in Xenopus ooctyes.

90 tress bidirectional interplay and identifies alpha7 nAChRs as a promising therapeutic target for stre

91 Here we identify alpha7 nAChR as a key regulator of CFTR in the airways.

92 ative conditions; this could be explained if alpha7-nAChRs buffer ACh and regulate its availability t

93 These data further implicate alpha7 nAChRs in regulation of aggression, and demonstra

94 (an alpha7 nAChR agonist), and was absent in alpha7 nAChR knock-out mice.

95 nd NIC intake, suggesting that a decrease in alpha7 nAChR function increases motivation to work for N

96 For deletions, this decrease in alpha7 nAChR-dependent calcium flux is expected due to h

97 0 ms prior to SC stimulation, it resulted in alpha7 nAChR-dependent long-term potentiation (LTP) or s

98 In contrast, mutations of Tyr-195 in alpha7-nAChR led to decreased activation by nicotine wit

99 dy was aimed at addressing which residues in alpha7-nAChRs potentially interact with Abeta to regulat

100 in the plasma of average smokers) increased alpha7-nAChR levels in human SCC-L cell lines.

101 tanus toxin to individual synapses increases alpha7-nAChR dwell time at presynaptic sites.

102 nAChRs by demonstrating that choline-induced alpha7 nAChR currents were present in Cre-negative, but

103 Abeta exposure-induced alpha7-nAChR functional upregulation occurs before there

104 up- and downregulation of anti-inflammatory alpha7 nAChR on colonic CD4 T cells induced by cytokines

105 oreover, expression of the anti-inflammatory alpha7-nAChR (alpha7-nicotinic acetylcholine receptor) w

106 imits for intoxication in humans can inhibit alpha7 nAChRs in LDTg neurons from rats.

107 a well characterized conotoxin that inhibits alpha7 nAChRs, on differentiated THP-1 pre-monocyte macr

108 This novel mechanism involving alpha7-nAChRs in mediation of Abeta effects provides pot

109 ed decay times of pharmacologically isolated alpha7-nAChR- and alpha3*-nAChR-EPSCs.

110 ed the baboon brain and specifically labeled alpha7-nAChR.

111 red the mouse brain and specifically labeled alpha7-nAChRs.

112 As a result, mice lacking alpha7-nAChRs have an altered balance in the excitatory/

113 ing nAChRs, but through distinct mechanisms: alpha7-nAChRs affect only the termination of spontaneous

114 study the key aromatic residues in the mouse alpha7-nAChR agonist-binding pocket.

115 Agonist-induced responses of Tyr-93 mutant alpha7-nAChRs indicated possible interactions of nicotin

116 ibuted alpha7- and alpha3-containing nAChRs (alpha7-nAChRs and alpha3*-nAChRs).

117 The mouse blocking studies with non-alpha7-nAChR central nervous system drugs demonstrated t

118 Our results suggest that non-alpha7-nAChRs such as alpha3*-nAChRs may be suitable for

119 ctivation of presynaptic alpha4beta2 but not alpha7 nAChRs in the DRN.

120 al processing involves alpha4beta2*, but not alpha7, nAChRs, whereas both receptor subtypes regulate

121 ow that the effects of beta2-nAChRs, but not alpha7-nAChRs, are mediated through the activation of GA

122 We also observed alpha7 nAChR-mediated calcium rises at mossy fiber giant

123 nged nicotine exposure mimics the absence of alpha7 nAChR in mice or its inactivation in vitro in hum

124 oth orthosteric and allosteric activation of alpha7 nAChR require cooperative activity at the interfa

125 Methyllycaconitine (MLA), an antagonist of alpha7 nAChR, could efficiently block these pathogenic e

126 ly, electrophysiological characterization of alpha7 nAChR-mediated current traces was similar in term

127 permitted the discovery of a novel class of alpha7 nAChR agonists with improved selectivity, in part

128 The functional coupling of alpha7 nAChR to CFTR occurs through Ca(2+) entry and act

129 ted by RT-PCR and cell surface expression of alpha7 nAChR is detected by confocal microscopy and flow

130 s the pro-cognitive therapeutic potential of alpha7 nAChR agonists.

131 These data identify reduction of alpha7 nAChR function as a potential mechanism for eleva

132 ts demonstrate the anti-inflammatory role of alpha7 nAChR in NK cells and suggest that modulation of

133 This study establishes the potential role of alpha7 nAChR in the regulation of CFTR function and in t

134 dels of BBB were used to dissect the role of alpha7 nAChR in up-regulation of Abeta induced by gp120,

135 schizophrenia are evident through the use of alpha7 nAChR agonists, while positive allosteric modulat

136 chizophrenia and also identify activation of alpha7 nAChRs as a potential strategy for tobacco cessat

137 Our findings indicate that activation of alpha7 nAChRs at presynaptic sites, via a mechanism invo

138 ifferences in the mechanism of activation of alpha7 nAChRs by ACh and 4BP-TQS.

139 nificant depressed through the activation of alpha7 nAChRs localized on the TSC and activated by the

140 creasing glutamate release via activation of alpha7 nAChRs on the glutamate terminals, suggesting a c

141 These data indicate that activation of alpha7 nAChRs was both necessary and sufficient to enhan

142 etermine whether pharmacological blockade of alpha7 nAChRs would increase motivation of rats to intra

143 In the case of alpha7 nAChRs, ACh causes rapid activation and almost co

144 ngly, the main single-channel conductance of alpha7 nAChRs, was significantly larger when activated b

145 Here, we demonstrate that direct coupling of alpha7 nAChRs to G proteins enables a downstream calcium

146 ghts into themechanism of desensitization of alpha7 nAChRs by providing evidence that the lipid compo

147 rates of smoking, have reduced expression of alpha7 nAChRs and may particularly benefit from this com

148 cells that naturally express high levels of alpha7 nAChRs, such as neurons in the hippocampus and hy

149 unctional, cell- and tissue-specific loss of alpha7 nAChRs by demonstrating that choline-induced alph

150 ent type I positive allosteric modulators of alpha7 nAChRs that may have therapeutic value in restori

151 1b represents the most potent ago-PAM of alpha7 nAChRs available to date and is considered for fu

152 In contrast, stimulation of alpha7 nAChRs by acetylcholine may mediate the increased

153 armacological properties similar to those of alpha7 nAChRs, although amplitudes of alpha7beta2 nAChR-

154 Analysis of alpha7-nAChR function in hippocampal interneurons in cul

155 s a potential PET radioligand for imaging of alpha7-nAChR in non-human primates.

156 We also observed that the levels of alpha7-nAChR in human SCC-L tumors (isolated from patien

157 Nicotine increased the levels of alpha7-nAChR mRNA and alpha7-nAChR transcription in huma

158 depends on the second intracellular loop of alpha7-nAChR subunits, and is specific in that it does n

159 ion triggers rapid calcium-dependent loss of alpha7-nAChR clusters.

160 ble imaging properties for quantification of alpha7-nAChR in the human brain.

161 Nicotine-induced up-regulation of alpha7-nAChR required GATA4 and GATA6.

162 Nicotine-induced up-regulation of alpha7-nAChR was confirmed in vivo by chicken chorioalla

163 y, CXCR4 activation induces up-regulation of alpha7-nAChR, causing cell death, suggesting that alpha7

164 nk is required for PMCA2-mediated removal of alpha7-nAChR clusters.

165 agonist binding domain for the activation of alpha7-nAChRs by Abeta.

166 Similarly, nicotinic activation of alpha7-nAChRs in WT organotypic culture, as well as cell

167 avioral analysis, we show that activation of alpha7-nAChRs increases in the rat VTA both the tyrosine

168 th impulsivity and locomotor activity and of alpha7-nAChRs in hypothalamic regions associated with ar

169 Blockade of alpha7-nAChRs markedly reduced, whereas low-dose stimula

170 ndogenous PPARalpha ligands are effectors of alpha7-nAChRs and that their neuromodulatory properties

171 ositron emission tomography (PET) imaging of alpha7-nAChRs.

172 g are effects on the immobile populations of alpha7-nAChRs and alpha3*-nAChRs.

173 such SCC-L patients) causes up-regulation of alpha7-nAChRs, which facilitates tumor growth and progre

174 eptor, induces a functional up-regulation of alpha7-nAChRs.

175 ivity and perhaps functional upregulation of alpha7-nAChRs are necessary for production of Abeta-indu

176 ceptor, its "non-classical" binding sites on alpha7 nAChR should be within the extracellular domain.

177 agonist activity but retain PAM activity on alpha7 nAChRs, demonstrating the importance of the locat

178 led five distinct pharmacological effects on alpha7 nAChRs.

179 dupDeltaalpha7 as well as their influence on alpha7 nAChRs may help explain the pathophysiology of sc

180 ng with the allosteric transmembrane site on alpha7 nAChRs.

181 ylation state of GluA1 which is dependent on alpha7-nAChR and intracellular calcium.

182 explores the effect of nicotine exposure on alpha7-nAChR levels in squamous cell carcinoma of the lu

183 The dependence on alpha7-nAChRs becomes clear when comparing wild-type (WT

184 iral-mediated downregulation of the beta2 or alpha7 nAChR subunit in the amygdala all induced robust

185 e regulated in part by either alpha4beta2 or alpha7 nAChRs.

186 nt may result from perturbed alpha3*- and/or alpha7-nAChR function.

187 pha4beta2-nAChRs, but not on alpha4beta4- or alpha7-nAChRs, suggesting nAChR subunit selectivity of o

188 In addition, nicotine and PNU282987 (alpha7-nAChR agonist) accelerated the growth of the chol

189 and schizophrenia, and drugs that potentiate alpha7 nAChRs through the regulation of desensitization

190 Pharmacotherapies potentiating alpha7 nAChR signaling have also been shown to reduce ag

191 bited the effects of nicotine at presynaptic alpha7 nAChRs on glutamate terminals in the mediodorsal

192 d in a decrease in activation of presynaptic alpha7-nAChRs by ACh and Abeta but with no change in res

193 Additional immobilization of presynaptic alpha7-nAChRs by antibody crosslinking increases glutama

194 reduction in both protomers almost prevents alpha7 nAChR recognition.

195 8.0) in control mice is superior to previous alpha7-nAChR PET radioligands.

196 f cholangiocarcinoma cell lines and promoted alpha7-nAChR-dependent activation of proliferation and p

197 Rather, alpha7 nAChR activation induced expression of c-Fos and

198 For this reason, alpha7 nAChR agonists represent promising therapeutic ca

199 ugh Alpha7 nicotinic acetylcholine receptor (alpha7 nAChR).

200 the alpha7 nicotinic acetylcholine receptor (alpha7*nAChR), has been implicated as a candidate gene i

201 ric alpha7 nicotinic acetylcholine receptor (alpha7-nAChR) as one possible functional target for pico

202 the alpha7-nicotinic acetylcholine receptor (alpha7-nAChR) subtype.

203 he alpha-7 nicotinic acetylcholine receptor (alpha7-nAChR), a potential therapeutic target for centra

204 the alpha7 nicotinic acetylcholine receptor (alpha7-nAChR), was more highly expressed in human cholan

205 The alpha7-nicotinic cholinergic receptor (alpha7-nAChR) is a key mediator of brain communication a

206 Alpha-7 nicotinic acetylcholine receptors (alpha7 nAChR) are implicated in the modulation of many c

207 ng alpha7 nicotinic acetylcholine receptors (alpha7 nAChR) may facilitate the specific modulation of

208 th alpha7 nicotinic acetylcholine receptors (alpha7 nAChR) on immunocompetent cells to inhibit cytoki

209 alpha7 Nicotinic acetylcholine receptors (alpha7 nAChR) represent promising therapeutic candidates

210 or alpha7-nicotinic acetylcholine receptors (alpha7-nAChRs) (Ki = 0.4-20 nM) has been synthesized for

211 ontaining nicotinic acetylcholine receptors (alpha7-nAChRs), capable of promoting transmitter release

212 in alpha7 nicotinic acetylcholine receptors (alpha7-nAChRs).

213 sive, or 'serenic,' an effect which requires alpha7 nAChRs and is recapitulated by GTS-21, an alpha7

214 infusion of 0, 10, or 40 nmol of a selective alpha7 nAChR agonist, PNU 282987, into these brain areas

215 nfusions of 0, 10, or 20 pmol of a selective alpha7 nAChR antagonist, alpha-conotoxin ArIB [V11L,V16D

216 This effect was attenuated by selective alpha7 nAChR antagonists or by chelation of extracellula

217 ct of long-term treatment with the selective alpha7 nAChR agonist A-582941 in aged 3xTg-AD mice with

218 This effect was blocked by the selective alpha7 nAChR antagonist methyllycaconitine (MLA).

219 ent by nicotine was inhibited by a selective alpha7-nAChR antagonist methyllycaconitine (MLA) and int

220 Since alpha7 nAChRs are present on neurons and glia (including

221 timulated NK cells to PNU-282987, a specific alpha7 nAChR agonist, increases intracellular calcium co

222 Specifically, alpha7-nAChR up-regulation is observed in mouse striatum

223 encoding three requisite receptor subtypes: alpha7-nAChR, alpha4beta2-nAChR, and a serotonin recepto

224 ty receptors (containing the alpha7-subunit, alpha7-nAChRs) can regulate cortical network function ex

225 ime is a species containing alpha7 subunits (alpha7-nAChRs).

226 contain alpha7 nicotinic receptor subunits (alpha7-nAChRs).

227 found that TCR stimulation decreased surface alpha7 nAChRs and reduced single-channel conductance.

228 ed understanding of this novel way to target alpha7 nAChR therapeutically.

229 milar snake alpha-neurotoxins also targeting alpha7 nAChR.

230 imes more pronounced for alpha3*-nAChR- than alpha7-nAChR-mediated currents and operated over a consi

231 We also determined that alpha7 nAChR binding sites were absent on GFAP-positive

232 d from intracellular stores, indicating that alpha7 nAChR is functional.

233 Here, we showed that alpha7 nAChR-dependent calcium signal cascades are downr

234 ignificantly reduced by MLA, suggesting that alpha7 nAChR may play an important role in neuropatholog

235 Evidence suggests that alpha7 nAChR activation impacts rule acquisition and ini

236 We propose that alpha7 nAChRs coordinate pre- and postsynaptic activitie

237 In recent studies we show that alpha7 nAChRs bind signaling proteins such as heterotrim

238 poly(I:C) stimulation only, indicating that alpha7-nAChR, a highly Ca(2+) permeable ion channel sens

239 We additionally show that alpha7-nAChR stimulation is needed for NMDA actions, sug

240 7-nAChR, causing cell death, suggesting that alpha7-nAChR is a previously unrecognized contributor to

241 e for paracrine nicotinic signaling but that alpha7-nAChRs may not be suitable.

242 tional proteomics on rat brain, we show that alpha7-nAChRs are associated with plasma membrane calciu

243 Here we show that alpha7-nAChRs unexpectedly promote formation of glutamat

244 Our results further suggest that alpha7-nAChRs may buffer ACh and regulate its bioavailab

245 The alpha7 nAChR subtype is highly expressed in the laterodo

246 The alpha7 nAChR-positive allosteric modulator PNU120596 [N-

247 milar to that of alphaCT-alphaCT against the alpha7 nAChR and is more active against alpha3beta2 nACh

248 8A, however, did significantly attenuate the alpha7 nAChR-induced Galphaq calcium signaling response

249 ies the mechanism of desensitization for the alpha7 nAChR.

250 These findings identify the alpha7 nAChR as an important regulator of aggressive beh

251 A mutation of the GPBC in the alpha7 nAChR (alpha7345-348A) abolishes interaction with

252 or different allosteric binding sites in the alpha7 nAChR and paves the way for future development of

253 nAChR and chimeric receptor composed of the alpha7 nAChR extracellular ligand-binding domain and the

254 nerated mice in which the fourth exon of the alpha7 nAChR gene (Chrna7) is flanked by loxP sites (B6-

255 ain with the structural determination of the alpha7 nAChR glycosylation site.

256 rophages and supports the involvement of the alpha7 nAChR in regulating the inflammatory response via

257 s that the anti-inflammatory activity of the alpha7 nAChR is mediated by a signal transduction pathwa

258 Lastly we found that the presence of the alpha7 nAChR subtype to both pre- and postsynaptic sites

259 ) a potent and selective full agonist of the alpha7 nAChR that demonstrated improved plasma stability

260 4, WAY-361789), a novel, full agonist of the alpha7 nAChR that was evaluated in vitro and in vivo.

261 ed as potent and selective modulators of the alpha7 nAChR with favorable in vitro safety profiles and

262 mically related allosteric modulators of the alpha7 nAChR.

263 to resemble the ligand-binding domain of the alpha7 nAChR.

264 d provide a new chemical space to target the alpha7 nAChR.

265 Here we show that in contrast to the alpha7 nAChR, the alpha7beta2 nAChR is highly susceptibl

266 to evidence that these PAMs bind within the alpha7 nAChR transmembrane region, we generated and vali

267 ma membrane can modulate the activity of the alpha7 nAChRs.

268 suggesting again a presynaptic action of the alpha7 nAChRs.

269 Expression of the alpha7*nAChR mRNA and protein are reduced in multiple re

270 The alpha7-nAChR selective ligand 1 (SSR180711) blocked the

271 ASEM is an antagonist for the alpha7-nAChR with high binding affinity (Ki = 0.3 nM).

272 thin this series exhibit specificity for the alpha7-nAChR, showing no activation or antagonism of alp

273 T) mice with mice constitutively lacking the alpha7-nAChR gene.

274 confirming a remarkable up-regulation of the alpha7-nAChR in gp120-transgenic mice brains.

275 AChBP showed only two to be agonists on the alpha7-nAChR below 10 muM concentration.

276 the binding of GATA4 or GATA6 to Sp1 on the alpha7-nAChR promoter, thereby inducing its transcriptio

277 compounds in complex mixtures targeting the alpha7-nAChR.

278 The alpha7-nAChRs expressed on HRMECs upregulate levels of M

279 RNA interference demonstrates that the alpha7-nAChRs must be expressed in the neuron being inne

280 dings do not support further testing of this alpha7 nAChR PAM compound for possible efficacy in smoki

281 his study suggest that nicotine acts through alpha7-nAChR and plays a novel role in the pathogenesis

282 Thus, alpha7 nAChR agonists appear to be a promising therapeut

283 Thus, alpha7 nAChRs are likely important mediators of the moto

284 Direct activation is sensitive to alpha7 nAChR antagonist methyllycaconitine, although the

285 results also explain why genetic insults to alpha7-nAChR would profoundly disrupt cognitive experien

286 tionally revealed direct binding of Abeta to alpha7-nAChRs and to the Tyr-188 mutant receptor.

287 application data revealed that for wild-type alpha7 nAChR, the 3-furan desensitized state was relativ

288 S) that display similar effects on wild-type alpha7 nAChRs.

289 etylcholine efficacy) at alpha7beta2- versus alpha7-nAChRs.

290 tically depends on cholinergic signaling via alpha7 nAChR.

291 recording all reveal synaptic deficits when alpha7-nAChR input is absent.

292 alpha3*-nAChRs report more spillover when alpha7-nAChRs are competitively blocked than under nativ

293 subsequently examined the hippocampus, where alpha7 nAChRs are highly expressed, particularly in GABA

294 Further, whereas alpha7 nAChR subunit knockdown was somewhat more effecti

295 However, the mechanisms by which alpha7 nAChRs are regulated are poorly understood.

296 gions and potential neural circuits in which alpha7 nAChRs regulate aggressive behavior in male mice.

297 ew homeostatic regulatory mechanism in which alpha7-nAChR restrain may be adjusted as needed at presy

298 illover and postsynaptic potentiation, while alpha7-nAChR currents are prolonged probably for other r

299 naptic density-95), which is associated with alpha7-nAChRs and constrains their mobility as revealed

300 18)F-ASEM in the brain regions enriched with alpha7-nAChRs was 80%-90%.