Abstract
We have used radioligand binding studies to determine the affinities of seven bisindolylmaleimide analogues, six of which are selective inhibitors of protein kinase C, at human muscarinic M1-M4 receptors. The compounds were most potent at M1 receptors, and Ro-31-8220 was the most potent analogue, with a Kd of 0.6 microM at M1 receptors. The weakest compounds, bisindolylmaleimide IV and bisindolylmaleimide V, had Kd values of 100 microM. If it is necessary to use protein kinase C inhibitors at concentrations of 10 microM or more in studies involving muscarinic receptors then bisindolylmaleimide IV may be the most appropriate inhibitor to use.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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CHO Cells
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Cricetinae
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Enzyme Inhibitors / chemistry
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Enzyme Inhibitors / metabolism*
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Enzyme Inhibitors / pharmacology
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Humans
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Indoles / chemistry
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Indoles / metabolism*
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Indoles / pharmacology
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Maleimides / chemistry
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Maleimides / metabolism*
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Maleimides / pharmacology
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Muscarinic Antagonists / pharmacology
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Protein Kinase C / antagonists & inhibitors
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Radioligand Assay
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Receptors, Muscarinic / classification
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Receptors, Muscarinic / drug effects
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Receptors, Muscarinic / genetics
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Receptors, Muscarinic / metabolism*
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Recombinant Proteins / metabolism
Substances
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Enzyme Inhibitors
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Indoles
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Maleimides
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Muscarinic Antagonists
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Receptors, Muscarinic
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Recombinant Proteins
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Protein Kinase C
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bisindolylmaleimide I
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bisindolylmaleimide
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Ro 31-8220