Abstract:
:Cyclic nucleotide analogs were used to study relaxation of pig coronary arteries and guinea pig tracheal smooth muscle in an attempt to determine the roles of cAMP- and cGMP-dependent protein kinases (cA-K and cG-K). In pig coronary artery strips, cGMP analogs were generally more effective than cAMP analogs in promoting relaxation of K+-induced contractions. Significant relaxation of this tissue was caused primarily by those cyclic nucleotide analogs that had high affinities for purified cG-K but not for cA-K. The low potencies of cA-K-specific analogs, as compared with cG-K-specific analogs, could not be readily explained by either unusually high susceptibilities to phosphodiesterases or low partition coefficients. The most potent cGMP analog, 8-(4-chlorophenylthio)-cGMP, exhibited a very slow reversibility of its relaxant effects in the intact tissue, consistent with its strong resistance to hydrolysis by phosphodiesterases measured in vitro. Pig coronaries contained atypically high levels of cGMP and cG-K, implying a potentially important role of this enzyme in smooth muscle function. Carbamylcholine-induced contractions of guinea pig tracheal segments were more sensitive than K+-induced pig coronary artery contractions to relaxation by cyclic nucleotide analogs. Consequently, the number of analogs that could be studied was significantly expanded. The cGMP analogs were again generally more potent, and the effectiveness of both cGMP and cAMP analogs in relaxing this preparation correlated with the Ka of the analogs for in vitro activation of cG-K, but not cA-K. A particularly strong correlation was observed when the effects of analogs modified only at the C-8 position were examined. A known target enzyme of cA-K, phosphorylase, was not activated by cG-K-specific analogs but was activated by high concentrations of the cA-K-specific analogs. Studies using cyclic nucleotide analogs support a role for cG-K, but not for cA-K, in decreasing smooth muscle tone.
journal_name
Mol Pharmacoljournal_title
Molecular pharmacologyauthors
Francis SH,Noblett BD,Todd BW,Wells JN,Corbin JDsubject
Has Abstractpub_date
1988-10-01 00:00:00pages
506-17issue
4eissn
0026-895Xissn
1521-0111journal_volume
34pub_type
杂志文章abstract::Cross-talk between G protein-coupled receptors and protein tyrosine kinases is well established, but the phenotypic consequences of these signaling interactions are not completely understood. To investigate the role of Src family kinases in mitogenic signaling by G protein-coupled receptors, we used genetic and pharma...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.104.010546
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journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1995-01-01 00:00:00
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journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1993-08-01 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
doi:
更新日期:1990-12-01 00:00:00
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journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1992-02-01 00:00:00
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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:1989-05-01 00:00:00
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pub_type: 杂志文章
doi:
更新日期:1998-05-01 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:1993-09-01 00:00:00
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更新日期:2004-05-01 00:00:00
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journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1991-09-01 00:00:00
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journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1993-09-01 00:00:00
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journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1994-12-01 00:00:00
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journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1995-08-01 00:00:00
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journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1992-12-01 00:00:00
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journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1988-07-01 00:00:00
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journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1982-03-01 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
pub_type: 杂志文章
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更新日期:1997-02-01 00:00:00
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journal_title:Molecular pharmacology
pub_type: 杂志文章
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更新日期:1994-10-01 00:00:00