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Abstract

H-7, a protein kinase C inhibitor, inhibits phorbol ester-caused ornithine decarboxylase induction but fails to inhibit phorbol ester-caused suppression of epidermal growth factor binding in primary cultured mouse epidermal cells.

T Nakadate, S Yamamoto, E Aizu, K Nishikawa and R Kato
Molecular Pharmacology December 1989, 36 (6) 917-924;
T Nakadate
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S Yamamoto
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E Aizu
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K Nishikawa
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R Kato
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Abstract

12-O-tetradecanoylphorbol-13-acetate (TPA) induced ornithine decarboxylase (ODC) and suppressed 125I-epidermal growth factor (EGF) binding in primary cultured mouse epidermal cells. TPA (30 nM)-caused ODC induction was almost completely blocked by 30 microM H-7 [1-(5-isoquinolinylsulfonyl)-2-methylpiperazine], a well known protein kinase C inhibitor, but the same concentration of H-7 failed to restore the 125I-EGF binding suppressed by TPA (10 nM). On the other hand, sphingosine, another protein kinase C inhibitor, blocked not only TPA-caused ODC induction but also TPA-caused suppression of 125I-EGF binding. Concentration-response curves of sphingosine for these two TPA-caused cellular responses were almost identical. 1,2-Diacylglycerols such as 1,2-dioctanoylglycerol (30-300 microM) and 1-oleoyl-2-acetylglycerol (OAG) (30-300 microM) mimicked TPA actions. Similar to the case of TPA, suppression of 125I-EGF binding by OAG was barely inhibited by H-7, whereas sphingosine was more effective in inhibiting the OAG-caused suppression of 125I-EGF binding than was H-7. In TPA (50 nM)-pretreated epidermal cells, TPA (10 nM) failed to suppress 125I-EGF binding. H-7 (30 microM) did not affect TPA (30 nM)-caused translocation of protein kinase C. These results clearly demonstrate the differential inhibition by H-7 of the TPA-caused cellular responses and indicate that TPA-caused suppression of 125I-EGF binding to epidermal cells is mediated through protein kinase C function, which is barely inhibited by H-7.

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Molecular Pharmacology
Vol. 36, Issue 6
1 Dec 1989
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Abstract

H-7, a protein kinase C inhibitor, inhibits phorbol ester-caused ornithine decarboxylase induction but fails to inhibit phorbol ester-caused suppression of epidermal growth factor binding in primary cultured mouse epidermal cells.

T Nakadate, S Yamamoto, E Aizu, K Nishikawa and R Kato
Molecular Pharmacology December 1, 1989, 36 (6) 917-924;

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Abstract

H-7, a protein kinase C inhibitor, inhibits phorbol ester-caused ornithine decarboxylase induction but fails to inhibit phorbol ester-caused suppression of epidermal growth factor binding in primary cultured mouse epidermal cells.

T Nakadate, S Yamamoto, E Aizu, K Nishikawa and R Kato
Molecular Pharmacology December 1, 1989, 36 (6) 917-924;
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