Abstract：
:We have performed a systematic mutagenesis of three hydrophobic rings (17', 13' and 9') within transmembrane region (TM) 2 of the alpha9alpha10 nicotinic cholinergic receptor (nAChR) to a hydrophilic (threonine) residue and compared the properties of mutant receptors reconstituted in Xenopus laevis oocytes. Phenotypic changes in alpha9alpha10 mutant receptors were evidenced by a decrease in the desensitization rate, an increase in both the EC(50) for ACh as well as the efficacy of partial agonists and the reduction of the allosteric modulation by extracellular Ca(2+). Mutated receptors exhibited spontaneous openings and, at the single-channel level, an increased apparent mean open time with no major changes in channel conductance, thus suggesting an increase in gating of the channel as the underlying mechanism. Overall, the degrees of the phenotypes of mutant receptors were more overt in the case of the centrally located V13'T mutant. Based on the atomic model of the pore of the electric organ of the Torpedo ray, we can propose that the interactions of side chains at positions 13' and 9' are key ones in creating an energetic barrier to ion permeation. In spite of the fact that the roles of the TM2 residues are mostly conserved in the distant alpha9alpha10 member of the nAChR family, their mechanistic contributions to channel gating show significant differences when compared to other nAChRs. These differences might be originated from slight differential intramolecular rearrangements during gating for the different receptors and might lead each nAChR to be in tune with their physiological roles.
journal_name
Br J Pharmacoljournal_title
British journal of pharmacologyauthors
Plazas PV,De Rosa MJ,Gomez-Casati ME,Verbitsky M,Weisstaub N,Katz E,Bouzat C,Elgoyhen ABdoi
10.1038/sj.bjp.0706224subject
Has Abstractpub_date
2005-08-01 00:00:00pages
963-74issue
7eissn
0007-1188issn
1476-5381pii
0706224journal_volume
145pub_type
杂志文章abstract：:1. We have investigated the role of endogenous nitric oxide on renal vascular reactivity in late pregnancy in in situ blood perfused kidneys of alpha-chloralose anaesthetized Wistar-Kyoto rats. Nitric oxide synthesis inhibition was achieved by intravenous administration of NG-nitro-L-arginine or NG-nitro-L-arginine me...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0701363
更新日期：1997-09-01 00:00:00
abstract：:Cannabinoid (CB1) receptor activation acts neuronally, reducing GI motility, diarrhoea, pain, transient lower oesophageal sphincter relaxations (TLESRs) and emesis, and promoting eating. CB2 receptor activation acts mostly via immune cells to reduce inflammation. What are the key questions which now need answering to ...
journal_title：British journal of pharmacology
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journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1986.tb10174.x
更新日期：1986-01-01 00:00:00
abstract：:1. The radioligand binding characteristics of the 3H-derivative of the novel 5-HT3 receptor antagonist BRL46470 were investigated and directly compared to the well characterized 5-HT3 receptor radioligand [3H]-granisetron, in tissue homogenates prepared from rat cerebral cortex/hippocampus, rat ileum, NG108-15 cells, ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
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abstract：:1. The effects of the putative gap junction uncoupler, 1-heptanol, on the neurogenic and myogenic contractile responses of guinea-pig vas deferens were studied in vitro. 2. Superfusion of 2.0 mM heptanol for 20-30 min produced the following reversible changes in the biphasic neurogenic contractile response (8 trials):...
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journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1993.tb13716.x
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journal_title：British journal of pharmacology
pub_type： 杂志文章,评审
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pub_type： 杂志文章
doi：10.1111/j.1476-5381.1993.tb13727.x
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journal_title：British journal of pharmacology
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doi：10.1038/sj.bjp.0707284
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journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0702421
更新日期：1999-03-01 00:00:00
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journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1994.tb13057.x
更新日期：1994-05-01 00:00:00
abstract：BACKGROUND AND PURPOSE:This study examined the antinociceptive effects of sinomenine in a rat model of postoperative pain. EXPERIMENTAL APPROACH:Male and female rats were subjected to a surgical incision in the right hind paw, and the von Frey filament test was used to measure mechanical hypersensitivity after drug or...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/bph.13470
更新日期：2016-05-01 00:00:00
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journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1985.tb12936.x
更新日期：1985-02-01 00:00:00
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journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1986.tb09496.x
更新日期：1986-05-01 00:00:00
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journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1996.tb15973.x
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pub_type： 杂志文章
doi：10.1111/j.1476-5381.1990.tb12106.x
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doi：10.1038/sj.bjp.0707411
更新日期：2007-10-01 00:00:00
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doi：10.1038/sj.bjp.0707345
更新日期：2007-08-01 00:00:00
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doi：10.1111/j.1476-5381.1991.tb12213.x
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journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0706239
更新日期：2005-07-01 00:00:00
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更新日期：2006-03-01 00:00:00
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journal_title：British journal of pharmacology
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更新日期：2013-10-01 00:00:00
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journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1975.tb07363.x
更新日期：1975-02-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Psychological stress exacerbates symptoms of urinary bladder dysfunction; however, the underlying brain mechanisms are unclear. We have demonstrated that centrally administered bombesin, a stress-related neuropeptide, facilitates the rat micturition reflex. Brain bombesin-like peptides modulate t...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/bph.13941
更新日期：2017-09-01 00:00:00
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pub_type： 杂志文章,评审
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更新日期：2015-08-01 00:00:00
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journal_title：British journal of pharmacology
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doi：10.1111/j.1476-5381.2010.00954.x
更新日期：2010-11-01 00:00:00
abstract：:1. TRPM2 is a Ca2+ -permeable nonselective cation channel activated by intracellular ADP-ribose (ADPR) and by hydrogen peroxide (H2O2). We investigated the modulation of TRPM2 activity by N-(p-amylcinnamoyl)anthranilic acid (ACA). ACA has previously been reported to inhibit phospholipase A2 (PLA2). 2. Using patch-clam...
journal_title：British journal of pharmacology
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更新日期：2006-06-01 00:00:00
