Abstract:
:This study describes experiments investigating the mechanism of activation of A1 adenosine receptors. Isolated rat fat cells were used as a cellular model. The A1 receptors of these cells were covalently labeled with the agonist photoaffinity label R-2-azido-N6-p-hydroxyphenylisopropyladenosine. The covalent incorporation of the label into the binding subunit of the receptor was verified by demonstration of specific labeling of a peptide with Mr = 35,000 by the radioiodinated label. Such covalent labeling followed by removal of label not covalently bound led to a concentration-dependent reduction of cellular cAMP levels. This persistent effect of covalent labeling occurred with an IC50 value of 9 nM compared to an IC50 value of 0.9 nM for the direct reduction of cAMP levels by the label. The affinity of the label was determined in binding experiments. The Ki value of 19 nM was about 20 times higher than the corresponding IC50 value of cAMP reduction. Finally, the comparison between covalent binding and its effects suggests that covalently labeled receptors were fully activated. The data are interpreted as evidence for a receptor activation according to the occupancy theory. The analysis of the various concentration-response curves reveals the presence of spare receptors, which can be demonstrated by the method of agonist photoaffinity labeling.
journal_name
Mol Pharmacoljournal_title
Molecular pharmacologyauthors
Lohse MJ,Klotz KN,Schwabe Usubject
Has Abstractpub_date
1986-10-01 00:00:00pages
403-9issue
4eissn
0026-895Xissn
1521-0111journal_volume
30pub_type
杂志文章abstract::A central axiom of ligand-receptor theory is that agonists bind more tightly to active than to inactive receptors. However, measuring agonist affinity in inactive receptors is confounded by concomitant activation. We identified a cysteine substituted mutant γ-aminobutyric acid type A (GABAA) receptor with unique chara...
journal_title:Molecular pharmacology
pub_type: 杂志文章
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journal_title:Molecular pharmacology
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journal_title:Molecular pharmacology
pub_type: 杂志文章
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journal_title:Molecular pharmacology
pub_type: 杂志文章
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更新日期:1993-10-01 00:00:00
abstract::Cell-penetrating peptides are amphipathic or cationic oligopeptides able to transport covalently attached cargoes across cell membranes. Peptide aptamers are polypeptide fragments of endogenous proteins that mimic and thus perturb interactions with other cellular proteins. Combining aptamer and CPP technology can gene...
journal_title:Molecular pharmacology
pub_type: 评论,杂志文章
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journal_title:Molecular pharmacology
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journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1993-12-01 00:00:00
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journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1991-11-01 00:00:00
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journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1993-07-01 00:00:00
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journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1992-10-01 00:00:00
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journal_title:Molecular pharmacology
pub_type: 杂志文章
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journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1989-07-01 00:00:00
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pub_type: 杂志文章
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journal_title:Molecular pharmacology
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journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1989-11-01 00:00:00
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journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1986-10-01 00:00:00
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journal_title:Molecular pharmacology
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journal_title:Molecular pharmacology
pub_type: 杂志文章
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更新日期:2001-04-01 00:00:00
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journal_title:Molecular pharmacology
pub_type: 杂志文章
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pub_type: 杂志文章
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journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1999-11-01 00:00:00
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journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1994-08-01 00:00:00
abstract::The microtubule-binding taxanes, docetaxel and cabazitaxel, are administered intravenously for the treatment of castration-resistant prostate cancer (CRPC) as the oral administration of these drugs is largely hampered by their low and highly variable bioavailabilities. Using a simple, rapid, and environmentally friend...
journal_title:Molecular pharmacology
pub_type: 杂志文章
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journal_title:Molecular pharmacology
pub_type: 杂志文章
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journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1983-09-01 00:00:00