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Biomedical subjects

J B Roberts

Publications and source records attributed to J B Roberts.

At least 55 records · Page 3Linked to original sources
PubMed1973

Influence of mitochondria on phospholipid synthesis in preparations from rat liver.

1. The addition of mitochondria to an incubation system containing the soluble and microsomal fractions of rat liver enhances severalfold the incorporation of each of ethanolamine, phosphorylethanolamine and CDP-ethanolamine into phosphatidylethanolamine. 2. In the presence of microsomal, mitochondrial and soluble fractions, CDP-ethanolamine exhibits the greatest initial rate of incorporation (approx. 6nmol/h per mg of protein), being slightly faster than that of phosphorylethanolamine (approx. 5nmol/h per mg of protein). Incorporation of ethanolamine proceeds very slowly for the first 20min and only after 30min gives rates approaching those of the other two precursors. 3. By using a substrate ;dilution' technique it was shown that in the reconstituted system the affinity of each of the enzymes for their respective substrates is very high: 10mum for ethanolamine, 25mum for phosphorylethanolamine and 5mum for CDP-ethanolamine. 4. Isolation of the mitochondrial and microsomal fractions from the medium after incubation together with phosphorylethanolamine showed that about 70% of the total radioactivity was present in the microsomal fraction and about 30% in the mitochondria after only 20min. Similar experiments with ethanolamine as precursor revealed that after 20min only about 15% of the total radioactivity was present in the mitochondria but that after 40min about 30% was present in this fraction. 5. Heating and phospholipase treatment of mitochondria, but not freeze-thawing, eliminated the stimulatory effect of mitochondria on phospholipid synthesis. 6. The reconstituted system exhibits an absolute requirement for Mg(2+) (2mm gave maximal rates) and is inhibited by very low concentrations of Ca(2+) (100mum-Ca(2+) produced half-maximal inhibition with 3mm-Mg(2+)). Further addition of Mg(2+) overcame the Ca(2+) inhibition, suggesting that the inhibitory effect is readily reversible. 7. The concept that modification of the Mg(2+)/Ca(2+) ratio is a means of controlling the rate of cellular phospholipid synthesis is introduced.

Animals↗
PubMed1970

Placental transfer of pyridostigmine in the rat.

1. Carbon-14 labelled pyridostigmine in single doses was given by intramuscular injection to pregnant rats, and maternal blood, foetal and placental homogenates were examined for total radioactive content, pyridostigmine and its metabolite, 3-hydroxy-N-methyl pyridinium.2. The level of radioactivity in all tissues was highest at 15 min and fell to negligible amounts at 24 hr. The concentrations in placenta were similar to those in maternal blood, but there was some indication of retention of radioactive drug in the placenta. The concentrations in the foetus were substantially lower, but the subsequent slow decline in concentration suggests that cumulation of the drug could occur with repeated doses.3. The percentage of metabolite in the foetus was considerably higher than in placenta and blood, and the possible reasons for this are discussed.

Animals↗
PubMed1969

Metabolism and exretion of 3-hydroxyphenyltrimethylammonium and neostigmine.

1. Carbon-14 labelled 3-hydroxyphenyltrimethylammonium (3-OH PTMA), an active metabolite of neostigmine, has been given to rats by intramuscular injection and its excretion, distribution and metabolism have been studied.2. A method is described for the separation and estimation of free and conjugated 3-OH PTMA in urine and liver.3. In the first hour, about 20% of a dose is excreted in the urine as free 3-OH PTMA and thereafter the rate of excretion of glucuronide conjugate exceeds that of free 3-OH PTMA. In 24 hr 76.8% of the dose is excreted in urine mainly as the conjugate.4. The peak concentration of radioactivity in blood occurs within 30 min and in liver within 1 hr after administration. More than 90% of the radioactivity in liver occurs as the glucuronide conjugate. Relatively high concentrations of radioactivity were found in liver and heart.5. In the hen 3-OH PTMA is rapidly excreted by renal tubular secretion.6. Experiments with carbon-14 labelled neostigmine show that up to 1 hr mainly unchanged neostigmine is excreted in urine; thereafter increasing amounts of free 3-OH PTMA and its glucuronide conjugate are excreted.7. It is concluded that the duration of action of neostigmine is determined by its rapid renal excretion and by its metabolism to the glucuronide conjugate of 3-OH PTMA.

Animals↗