Biochemical and ultrastructural studies on the effect of verapamil on formation and secretion of lipoproteins in rat hepatocyte suspensions

Abstract

The effect of the calcium channel blocker verapamil on structure, formation and secretion of very-low-density lipoproteins (VLDL) from rat hepatocytes in suspension was examined. After 30 min incubation at a verapamil dose of 200 microM neither free fatty acid (FFA) uptake nor triglyceride (TG) and phospholipid (PL) secretion into the incubation medium were significantly changed. After 90 min incubation the TG secretion was inhibited by about 60%, whereas the PL output was only insignificantly lowered, indicating the secretion of abnormally composed lipoprotein particles. Morphologically, after 30 min incubation the hepatocytes had lost their microvillous border and exhibited a 2-3-fold increase in volume density and average size of the lysosomes. In the Golgi-containing regions an accumulation of smooth-surfaced microvesicles was regularly evident. The configuration of the Golgi complexes was normal. After 90 min incubation the lysosomes showed a further significant elevation in volume and size. The Golgi complexes exhibited only minor changes, but their content in VLDL particles was reduced per microns 2 Golgi complex by about 75%. Commonly, the VLDL were larger and more heterogenous in size. The diameter of those VLDL secreted into the incubation medium ranged from 31 to 84 nm, thus surpassing the control values by 2-3 times. The secretion of large-sized VLDL was regularly associated with the intracytoplasmic appearance of dilated smooth-surfaced vesicles filled with size-modified VLDL. These vesicles were concentrated within Golgi-containing areas from where they were widely dispersed towards the cell periphery.(ABSTRACT TRUNCATED AT 250 WORDS)