Document Detail


Effect of calmodulin and protein kinase C inhibitors on globally ischemic rat hearts.
MedLine Citation:
PMID:  1381016     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Several calmodulin inhibitors have been reported to be cardioprotective, but the ability of these compounds to inhibit protein kinase C (PKC) suggests that calmodulin inhibition may not be the sole mechanism responsible. To distinguish between the effects, we determined the cardioprotective activity of several calmodulin inhibitors with differing PKC inhibitory potencies in isolated globally ischemic rat hearts. Twenty-five minutes of global ischemia caused significant myocardial dysfunction, contracture formation, and lactate dehydrogenase (LDH) release on reperfusion in vehicle-treated hearts. The calmodulin inhibitors trifluoperazine, W-7, calmidazolium, W-13, and CGS 9343B improved postischemic contractile function and/or reduced LDH release. They also reduced preischemic cardiac function, although cardioprotection did not appear to be correlated with cardiodepression. Calmodulin inhibitors increased preischemic coronary flow (CF) and decreased heart rate (HR), but controlling these parameters did not affect the cardioprotection. Pretreatment of ischemic hearts with trifluoperazine was associated with preservation of myocardial ATP. Pretreatment of ischemic rat hearts with the PKC inhibitors staurosporine, calphostin C, polymyxin B, and H-7 did not result in cardioprotection. Thus, calmodulin inhibition causes cardioprotection that appears to be independent of PKC inhibition.
Authors:
C A Sargent; P G Sleph; S Dzwonczyk; M A Smith; G J Grover
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Publication Detail:
Type:  In Vitro; Journal Article    
Journal Detail:
Title:  Journal of cardiovascular pharmacology     Volume:  20     ISSN:  0160-2446     ISO Abbreviation:  J. Cardiovasc. Pharmacol.     Publication Date:  1992 Aug 
Date Detail:
Created Date:  1992-10-01     Completed Date:  1992-10-01     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  7902492     Medline TA:  J Cardiovasc Pharmacol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  251-60     Citation Subset:  IM    
Affiliation:
Department of Pharmacology, Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, New Jersey 08543.
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MeSH Terms
Descriptor/Qualifier:
1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine
Alkaloids / pharmacology
Analysis of Variance
Animals
Benzimidazoles / pharmacology
Calmodulin / antagonists & inhibitors*
Coronary Disease / drug therapy*,  physiopathology
Heart / drug effects*
Isoquinolines / pharmacology
L-Lactate Dehydrogenase / blood
Male
Myocardial Contraction / drug effects
Naphthalenes*
Piperazines / pharmacology
Polycyclic Compounds / pharmacology
Polymyxin B / pharmacology
Protein Kinase C / antagonists & inhibitors*
Rats
Rats, Inbred Strains
Staurosporine
Sulfonamides / pharmacology
Trifluoperazine / pharmacology
Chemical
Reg. No./Substance:
0/Alkaloids; 0/Benzimidazoles; 0/Calmodulin; 0/Isoquinolines; 0/Naphthalenes; 0/Piperazines; 0/Polycyclic Compounds; 0/Sulfonamides; 109826-26-8/CGS 9343B; 117-89-5/Trifluoperazine; 121263-19-2/calphostin C; 1404-26-8/Polymyxin B; 62996-74-1/Staurosporine; 65595-90-6/W 7; 84477-87-2/1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; EC 1.1.1.27/L-Lactate Dehydrogenase; EC 2.7.11.13/Protein Kinase C

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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