A fluorescent protein kinase C inhibitor: 1-(1-hydroxy-5-isoquinolinylsulfonyl)piperazine.
The isoquinolinesulfonamide compound 1-(5-isoquinolinyl-sulfonyl)-2-methylpiperazine (H-7) has been widely used as a protein kinase C inhibitor. Although H-7 and its derivatives are useful for the demonstration of the biological function of protein kinase C or cyclic nucleotide-dependent protein kinases, these compounds are not available for a histological approach to protein kinase C. In the present study, we introduce 1-(1-hydroxy-5-isoquinolinylsulfonyl)piperazine (hydroxy H-7) as a useful tool in tissue experiments. The property of the compound as a protein kinase C inhibitor was similar to that of H-7. Hydroxy H-7 inhibited the enzyme in a competitive manner with ATP, the Ki value was 23 microM, and exhibited a fluorescence property with a maximum emission wavelength of 444 nm excited at 350 nm. Fluoromicroscopical investigations revealed that hydroxy H-7 penetrated the cell membrane and was distributed mainly in the cytoplasm.
Department of Pharmacology, Nagoya University School of Medicine, Japan.
M
M
Hagiwara
M
M
Inagaki
J
J
Takahashi
T
T
Yoshida
H
H
Hidaka
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D007546:Isoquinolines / Q000494:pharmacology*; D007614:Macropodidae; D010879:Piperazines / Q000494:pharmacology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D013050:Spectrometry, Fluorescence; D013056:Spectrophotometry, Ultraviolet
D007546:Isoquinolines; D010879:Piperazines; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000255:Adenosine Triphosphate; D011493:Protein Kinase C