Abstract
Tumor necrosis factor-alpha (TNF alpha) is a potentially powerful anti-neoplastic agent; however, its therapeutic usefulness is limited by its cardiotoxic and negative inotropic effects. Accordingly, studies were undertaken to gain a better understanding of the mechanisms of TNF alpha-mediated cardiodepression. Single cell RT-PCR, [125I]TNF alpha ligand binding and Western immunoblotting experiments demonstrated that rat cardiac cells predominantly express type I TNF alpha receptors (TNFRI or p60). TNF alpha inhibited cardiac L-type Ca2+ channel current (ICa) and contractile Ca2+ transients. Thus, it is possible that the negative inotropic effects of TNF alpha are the result of TNFRI-mediated blockade of cardiac excitation-contraction coupling.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Base Sequence
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Calcium / antagonists & inhibitors
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Calcium / metabolism
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Calcium Channels / metabolism
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DNA Primers / chemistry
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Fluorescent Dyes / metabolism
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Gene Expression / genetics
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Immunoblotting
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In Vitro Techniques
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Indoles / metabolism
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Molecular Sequence Data
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Myocardium / metabolism*
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Patch-Clamp Techniques
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Polymerase Chain Reaction
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RNA, Messenger / analysis
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RNA, Messenger / metabolism
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Rats
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Rats, Sprague-Dawley
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Receptors, Tumor Necrosis Factor / chemistry
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Receptors, Tumor Necrosis Factor / genetics
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Receptors, Tumor Necrosis Factor / metabolism*
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Tumor Necrosis Factor-alpha / pharmacology*
Substances
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Calcium Channels
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DNA Primers
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Fluorescent Dyes
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Indoles
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RNA, Messenger
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Receptors, Tumor Necrosis Factor
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Tumor Necrosis Factor-alpha
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indo-1
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Calcium