Occurrence of lysosomes and the differentiation of rat liver cells

Summary The occurrence of lysosomes has been investigated electron microscopically and cytochemically in cells of rat liver in the course of ontogenesis.It has been found that primary lysosomes occur during the whole period under investigation and that they originate from the Golgi complex. Some of them assume the appearance of multivesicular bodies. Acid phosphatase activity is lower at the prenatal stage than after the birth. The occurrence of secondary lysosomes proceeds in two stages. Secondary lysosomes appear in a high number at the beginning of differentiation of the liver diverticulum (10–12 day of embryonic life). On the subsequent days they are, with few exceptions, no more present. At the end of the embryonic period (starting with the 20th day) and especially after the birth, they progressively grow in number and move from the region of central cytoplasm peripherally towards the bile capillary.Differences in occurrence of secondary lysosomes are in connexion with reconstruction of the liver primordium at the beginning of liver development and with the change in metabolism of the liver cell after the birth.     

Effect of Antihypertensive Drugs on the “Intrinsic” Heart Rate

“Intrinsic” heart rate in man was measured by giving simultaneous atropine and propranolol and used to study the direct effect of antihypertensive drugs on the heart. Though the intrinsic and control heart rates decreased significantly following the administration of reserpine, there was no significant difference between high and low doses. No similar effects were observed with debrisoquine sulphate and methyldopa, though in high doses the latter produced a decrease which was of some statistical significance.     

Synthesis of 10,11-dihydrofarnesyl pyrophosphate from 6,7-dihydrogeranyl pyrophosphate by prenyltransferase

The syntheses of 6,7-dihydrogeraniol and of its pyrophosphate are described. It is shown that this analogue of geranyl pyrophosphate is a substrate for liver prenyltransferase and that the product synthesized by this enzyme from it and isopentenyl pyrophosphate is 10,11-dihydrofarnesyl pyrophosphate. The K(m) value for 6,7-dihydrogeranyl pyrophosphate was determined to be 1.11+/-0.19mum as compared with 4.34+/-1.71mum for geranyl pyrophosphate. The maximum reaction velocity with the artifical substrate was, however, only about one-fourth of that observed with geranyl pyrophosphate. The binding of isopentenyl pyrophosphate to the enzyme was not affected by the artificial substrate.     

Analogues of geranyl pyrophosphate as inhibitors of prenyltransferase

Six analogues of geranyl pyrophosphate (the monophosphates of geraniol and tetrahydrogeraniol, and the pyrophosphates of nerol, octan-1-ol, tetrahydrogeraniol and citronellol) were synthesized, and were found to be inhibitors of pig liver prenyl- (geranyl-)transferase. The effects of each analogue were analysed in kinetic experiments, which showed the pyrophosphates of citronellol, tetrahydrogeraniol and octan-1-ol to be the most potent inhibitors. The results are interpreted to support a previous hypothesis that the main forces in the binding of substrates to prenyltransferase are non-specific lipophilic forces and a pyrophosphate-binding force.