Abstract：
:Allosteric regulation of [3H]N-methylscopolamine [( 3H]NMS) and [3H]quinuclidinyl benzilate [( 3H]QNB) dissociation from the m1-m5 muscarinic receptor subtypes was examined in transfected CHO-K1 cells. Half-times of dissociation of [3H]NMS from cell membranes (at 23 degrees) ranged from less than 5 min for the m2 subtype to more than 60 min for the m5 subtype. For [3H]QNB, half-times (at 37 degrees) ranged from 1 hr (m2) to almost 4 hr (m3). The presence of gallamine slowed the dissociation of [3H]NMS from all of the subtypes, with an order of potency of m2 greater than m4 greater than m1 greater than m3 greater than m5. Dissociation of [3H]QNB from m1 and m2 receptors was modulated by gallamine in the biphasic manner that we have described previously for cardiac receptors; that is, low concentrations (1-10 microM) of gallamine accelerated dissociation, while 1 mM gallamine slowed it. Verapamil slowed the dissociation of [3H]-QNB from the m2 receptor in a monophasic manner, while the action of d-tubocurarine was qualitatively similar to that of gallamine. The potency of gallamine in allosterically regulating the m2 receptor was inversely related to ionic strength. Inactivation of pertussis toxin-sensitive G proteins abolished the ability of guanine nucleotides to regulate agonist affinity at the m2 receptor, but had no effect on allosteric regulation of the m2 receptor. These findings indicate that susceptibility to allosteric regulation varies in a complex way across muscarinic receptor subtypes and according to the choice of ligand.
journal_name
Biochem Pharmacoljournal_title
Biochemical pharmacologyauthors
Ellis J,Huyler J,Brann MRdoi
10.1016/0006-2952(91)90591-rsubject
Has Abstractpub_date
1991-10-24 00:00:00pages
1927-32issue
10eissn
0006-2952issn
1873-2968pii
0006-2952(91)90591-Rjournal_volume
42pub_type
杂志文章abstract：:Parkin (PRKN) is a ubiquitin E3 ligase that catalyzes the ubiquitination of several proteins. Mutations in the human Parkin gene, PRKN, leads to degeneration of dopaminergic (DA) neurons, resulting in autosomal recessive early-onset parkinsonism and the loss of PRKN function is linked to sporadic Parkinson's disease (...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
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journal_title：Biochemical pharmacology
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更新日期：1987-10-01 00:00:00
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更新日期：1993-05-25 00:00:00
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pub_type： 杂志文章
doi：10.1016/0006-2952(92)90269-o
更新日期：1992-01-22 00:00:00
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pub_type： 杂志文章
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更新日期：2000-12-15 00:00:00
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doi：10.1016/0006-2952(88)90724-1
更新日期：1988-01-15 00:00:00
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pub_type： 杂志文章
doi：10.1016/j.bcp.2018.03.011
更新日期：2018-06-01 00:00:00
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doi：10.1016/j.bcp.2005.09.022
更新日期：2005-12-05 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
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更新日期：1983-07-01 00:00:00
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更新日期：1989-04-15 00:00:00
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pub_type： 杂志文章
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更新日期：1996-07-12 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 历史文章,杂志文章
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更新日期：2008-07-01 00:00:00
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更新日期：2009-09-15 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章,评审
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更新日期：2009-06-15 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
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更新日期：1994-03-29 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
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更新日期：2003-11-01 00:00:00
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更新日期：1985-04-01 00:00:00
