Muscarinic interactions of bisindolylmaleimide analogues.
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.
Lazareno
S
S
MRC Collaborative Centre, London, UK. s-lazare@nimr.mrc.ac.uk
Popham
A
A
Birdsall
N J
NJ
D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D007211:Indoles / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D008301:Maleimides / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D018727:Muscarinic Antagonists / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D011869:Radioligand Assay; D011976:Receptors, Muscarinic / Q000145:classification / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism
D004791:Enzyme Inhibitors; D007211:Indoles; D008301:Maleimides; D018727:Muscarinic Antagonists; D011976:Receptors, Muscarinic; D011994:Recombinant Proteins; D011493:Protein Kinase C; C070515:bisindolylmaleimide I; C088060:bisindolylmaleimide; C064758:Ro 31-8220