Abstract:
:The activities of phosphorylase kinase and myosin light-chain kinase are regulated by Ca2+ binding to calmodulin. However, differences in the activation properties of the purified enzymes are apparent, since calmodulin binds to phosphorylase kinase in the absence of Ca2+ whereas prior formation of a Ca2+ . calmodulin complex is necessary for calmodulin to bind to and activate myosin light chain kinase. Since the phenothiazines have been implicated as anticalmodulin drugs and inhibit contractile activity in smooth muscle, we examined the effects of the phenothiazine, fluphenazine, on isometric tension development and phosphorylation of phosphorylase and the phosphorylatable light chain (P-light chain) of myosin in intact bovine tracheal smooth muscle. Preincubation with 50 microM fluphenazine for 5 min inhibited the maximal rate and extent of isometric tension development and P-light chain phosphorylation in the presence of 60 mM KCl. Application of fluphenazine after tension and the phosphate content of the P-light chain had reached steady-state levels in response to 60 mM KCl produced little relaxation or dephosphorylation of the P-light chain. KCl-mediated phosphorylase a formation was not inhibited by preincubation with fluphenazine for 5 min. However, long periods of preincubation (30-60 min) produced significant inhibition of phosphorylase a formation and proportionally greater inhibition of tension and P-light chain phosphorylation. Since phosphorylase a formation was not inhibited during short-term preincubation with fluphenazine, KCl-dependent increases in the concentration of free intracellular Ca2+ may not have been affected. Moreover, since both isometric tension development and P-light chain phosphorylation were attenuated in a parallel manner, inhibition of contractile activity in intact smooth muscle by anticalmodulin agents may be directly related to inhibition of P-light chain phosphorylation.
journal_name
Mol Pharmacoljournal_title
Molecular pharmacologyauthors
Silver PJ,Stull JTsubject
Has Abstractpub_date
1983-05-01 00:00:00pages
665-70issue
3eissn
0026-895Xissn
1521-0111journal_volume
23pub_type
杂志文章abstract::We examined the influence of the molecular structure of four novel adamantane derivatives on their ability to block the channels of nicotinic acetylcholine (ACh) and N-methyl-D-aspartate (NMDA) receptors. The structure of the drugs is Ad-CH2-N+H2-(CH2)5-R, where Ad is adamantane and R was varied from ammonium (IEM-175...
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
doi:
更新日期:1996-06-01 00:00:00
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journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1984-09-01 00:00:00
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journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1992-09-01 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:10.1124/mol.54.1.59
更新日期:1998-07-01 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
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更新日期:2008-11-01 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:1990-12-01 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:2002-11-01 00:00:00
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journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.109.055665
更新日期:2009-09-01 00:00:00
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journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1991-12-01 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
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更新日期:2008-06-01 00:00:00
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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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journal_title:Molecular pharmacology
pub_type: 杂志文章,评审
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更新日期:2004-11-01 00:00:00