Inhibition of wortmannin activities by amino compounds.
Wortmannin caused normal and strong inhibition on catecholamine secretion from bovine adrenal chromaffin cells and in vitro phosphoinositide 3-kinase activity in NaCl-, Na isethionate-, choline Cl-, Na acetate-, and N-acetyl glycine-based media. However, brief preincubation of wortmannin with the media containing amino compounds such as glutamate, aspartate, lysine, and glycine resulted in the prevention of the inhibitory effects of wortmannin on the above responses as two indexes of wortmannin activities. On the other hand, the amino compounds also caused several rapid changes in wortmannin medium; the changes in absorption spectrum of the medium; and the changes in the retention time of the peak on the HPLC chromatogram using a reverse-phase C-18 column and in the pattern of absorption spectrum of the peak. These changes were not observed in the cases of NaCl, Na isethionate, choline Cl, Na acetate or N-acetyl glycine. Another amino compound Tris, which was commonly used as a pH buffer, was unique in time course and induced the slow but parallel changes and reached maximal up to about 24h. These results taken together indicate that the amino compounds markedly inhibit the activities of wortmannin presumably through the binding of wortmannin to amino group.
Isosaki
Minoru
M
Department of Pharmacology, Nara Medical University, Kashihara, Nara 634-8521, Japan. misosaki@naramed-u.ac.jp
D000588:Amines / Q000494:pharmacology*; D000596:Amino Acids / Q000494:pharmacology; D000730:Androstadienes / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D002395:Catecholamines / Q000378:metabolism; D002417:Cattle; D019439:Chromaffin Cells / Q000187:drug effects / Q000378:metabolism; D003470:Culture Media / Q000737:chemistry; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D014325:Tromethamine / Q000494:pharmacology; D000077191:Wortmannin
D000588:Amines; D000596:Amino Acids; D000730:Androstadienes; D002395:Catecholamines; D003470:Culture Media; D004791:Enzyme Inhibitors; D014325:Tromethamine; D019869:Phosphatidylinositol 3-Kinases; D000077191:Wortmannin