Effects of perhexiline maleate on asialo-orosomucoid receptor endocytosis and recycling in HTC cells.
Perhexiline is a lysosomotropic agent which has proved to be very valuable to certain patients suffering from angina pectoris. However long-term administration of the drug may induce hepato- and neuro-toxicity. Using HTC cells (a rat hepatoma-derived cell line) whose plasma membranes were labeled with NaB[3H]4 after oxidation by NaIO4, endocytosis and recycling of labeled asialo-orosomucoid (ASOR) receptors were investigated in the presence of 50 mumols/l perhexiline maleate. The results demonstrate that the drug induces a significant decrease of the rate of both the internalization and the recycling of ASOR receptors. The mechanisms responsible for these effects have not yet been elucidated. However, the current findings may be related to the previously observed inhibitory effect of perhexiline on cellular (Na+, K+)-ATPase and Mg++-ATPase activities. Our findings would then reflect insufficient cellular energy production, resulting from depressed ATP hydrolysis in the presence of perhexiline.
Shacoori
V
V
Laboratoire de Biochimie Médicale B, Faculté de Médecine, Rennes, France.
Gueble-Val
F
F
Guenet
L
L
Blayau
M
M
Leray
G
G
Le Treut
A
A
Le Gall
J Y
JY
D000818:Animals; D037263:Asialoglycoprotein Receptor; D002478:Cells, Cultured; D004705:Endocytosis / Q000187:drug effects*; D007700:Kinetics; D009439:Neuraminidase / Q000494:pharmacology; D009961:Orosomucoid / Q000378:metabolism; D010480:Perhexiline / Q000494:pharmacology*; D051381:Rats; D011971:Receptors, Immunologic / Q000187:drug effects / Q000378:metabolism*
D037263:Asialoglycoprotein Receptor; D009961:Orosomucoid; D011971:Receptors, Immunologic; D009439:Neuraminidase; D010480:Perhexiline