Inhibition of apolipoprotein B net synthesis and secretion from cultured rat hepatocytes by the calcium-channel blocker diltiazem.
1. The effect of the Ca2+-channel blocker diltiazem on hepatic apolipoprotein B (apo B) synthesis and secretion was studied in 12-18 h cultures of collagenase-dispersed rat hepatocytes. 2. The presence of diltiazem in the medium decreased apo B secretion by hepatocytes in a concentration-dependent manner. At 25 microM, diltiazem inhibited apo B secretion by approx. 36%, but there was no evidence of intracellular accumulation of apo B. 3. The inhibition of apo B secretion by hepatocytes was significantly correlated with cell-associated diltiazem (r = 0.72, P less than 0.01). 4. The rate of apo B secretion remained linear over 16 h even in the presence of 50 microM-diltiazem. 5. At diltiazem concentrations in the medium which were inhibitory for apo B secretion, [14C]acetate incorporation into cellular lipids and [35S]methionine incorporation into protein were enhanced. 6. Diltiazem inhibited the secretion of the apo B variants with a preferential inhibition of the higher-molecular-mass form of apo B (apo BH) over the lower-molecular-mass form (apo BL) at diltiazem concentrations in the medium greater than 25 microM. 7. Together, these results suggest that Ca2+ may play an important role in the synthesis and secretion of apo B-containing lipoproteins.
Kwong
T C
TC
Department of Pathology, University of Rochester School of Medicine and Dentistry, NY 14642.
Sparks
J D
JD
Pryce
D J
DJ
Cianci
J F
JF
Sparks
C E
CE
D000085:Acetates / Q000378:metabolism; D000818:Animals; D001055:Apolipoproteins B / Q000096:biosynthesis* / Q000378:metabolism; D004110:Diltiazem / Q000378:metabolism / Q000494:pharmacology*; D007700:Kinetics; D008055:Lipids / Q000096:biosynthesis; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008970:Molecular Weight; D014176:Protein Biosynthesis; D051381:Rats; D011919:Rats, Inbred Strains
D000085:Acetates; D001055:Apolipoproteins B; D008055:Lipids; D004110:Diltiazem