Effects of mepanipyrim on intracellular trafficking: a comparative study on its effects on exocytic and endocytic trafficking of proteins, sphingolipids, and cholesterol.
Mepanipyrim, N-(4-methyl-6-prop-1-ynylpyrimidin-2-yl)aniline, diminished the cell surface expression of envelope glycoproteins of Newcastle disease and vesicular stomatitis viruses at concentrations where their synthesis was not profoundly affected. Intoxication by diphtheria toxin and ricin and recycling of transferrin were not affected even when cells were treated with mepanipyrim for 2 h before the addition of these probes, indicating that mepanipyrim does not act on the endocytic and recycling pathways of these proteins. Metabolic conversion of C6-NBD-ceramide to sphingomyelin and its back-exchange to the medium was also not affected, but synthesis and back-exchange of C6-NBD glucosylceramide were greatly influenced, and an accumulation of LDL-derived, unesterified cholesterol was induced by the drug. These results are discussed relating to the site(s) of action of mepanipyrim.
Miura
I
I
Microbial Toxicology Laboratory, Institute of Physical and Chemical Research (RIKEN), Saitama, Japan.
Muroi
M
M
Shiragami
N
N
Yamaguchi
I
I
Takatsuki
A
A
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002460:Cell Line; D002784:Cholesterol / Q000502:physiology*; D006224:Cricetinae; D004705:Endocytosis / Q000187:drug effects; D005089:Exocytosis / Q000187:drug effects; D005659:Fungicides, Industrial / Q000494:pharmacology*; D015726:Giant Cells / Q000187:drug effects; D006023:Glycoproteins / Q000096:biosynthesis; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D009521:Newcastle Disease / Q000378:metabolism; D011506:Proteins / Q000493:pharmacokinetics*; D011743:Pyrimidines / Q000494:pharmacology*; D013107:Sphingolipids / Q000493:pharmacokinetics*
D005659:Fungicides, Industrial; D006023:Glycoproteins; D008562:Membrane Glycoproteins; D011506:Proteins; D011743:Pyrimidines; D013107:Sphingolipids; D002784:Cholesterol; C104083:mepanipyrim