Effect of local anesthetics on plasma protein secretion by rat hepatocytes

The effects of some local anesthetics on plasma protein secretion by rat liver slices have been studied and have been compared with those of colchicine. Rat liver slices were pulse-labelled with l-[¹⁴C]leucine for 9 min at 37°C, collected on filter paper, washed with non-radioactive leucine and reincubated in the presence or absence of the drug to be tested. The radioactive plasma proteins produced were obtained by immunoprecipitation from either the chase medium or from the washed slices. Chlorpomazine, (3 · 10^?5 M), dibucaine (10^?5 M), lidocaine (10^?3 M) and procaine (5 · 10^?5 M) inhibited both the synthesis and secretion of plasma protein but did not affect the uptake of l-leucine into the slices nor the incorporation of phosphate into intracellular nucleotide phosphates or into phopholipids. The inhibition of secretion elicited by these drugs is probably not due to the inhibition of protein synthesis since cycloheximide, when added to the chase medium at a concentration which completely inhibits protein synthesis, did not inhibit plasma protein secretion, while cycloheximide plus procaine did inhibit secretion and also caused a retention of non-secreted plasma proteins within the slices. Unlike colchicine, howover, procaine did not cause the retained plasma proteins to accumulate in Goli-derived secretory vesicles, but showed a more general effect causing a distribution among several cell fractions.     

The influence of postnatal nutritional deprivation on the phospholipid content of developing rat lung.

It has been previously reported that fasting may result in decreased lung surfactant production. In order to investigate this relationship and the role of nutrition in lung phospholipid synthesis, 21-day-old rats were exposed for 60 h to one of five dietary regimens: standard rat chow (controls), fasting, pure glucose, pure fat, or pure protein. After the period of fasting there was a 33% decrease in lung protein content, but there was no change in DNA content. Exposure to any of the experimental diets resulted in a decrease in tissue total phospholipid and phosphatidylcholine content per lung, but not per unit lung protein. Similarly lung lavage phospholipid and phosphatidylcholine content was decreased by 25% after fasting when expressed per lung or per unit DNA, but not per unit protein. Pulmonary cholinephosphotransferase (EC 2.7.8.2) activity was decreased in the fasted animals and those fed the protein diet, but not in the glucose or fat-fed animals. The activities of acetyl-CoA carboxylase (EC 6.4.1.2) and microsomal fatty acid elongation were decreased in all the experimental groups except for the glucose-fed group. It is concluded that fasting results in a decrease in lung cell size but not in lung cell number. Total phospholipid and phosphatidylcholine content in lung tissue and lung lavage is decreased per cell but not per unit cell mass.     

Use of genetic analysis to test the potential role of serotonin in alcohol preference.

The hypothesis that alcohol preference in mice is influenced by brain serotonin levels was tested using genetic analysis. Alcohol preference and static serotonin content were assessed in C57BL/Ibg (alcohol-preferring) and DBA/2 (alcohol-avoiding) mice, as well as in Fl and F2 generations obtained by crossbreeding. The two parental strains showed dissimilar alcohol preferences but identical concentrations of brain serotonin. Serotonin concentration segregated independently of alcohol preference in the F1 and F2 generations. These data provides strong evidence against the hypothesis that brain serotonin content influences alcohol preference. However, they do not preclude the possibility that differential alcohol influences on serotonin metabolism or turnover rate may result in differing preference for a alcohol.     

Role of the serotoninergic raphe-hippocampus system for the antinocifensive effect of morphine

As revealed in earlier studies, the antinocifensive effect of morphine is brought about, among other things, with involvement of serotoninergic transmission mechanisms. In this context the role of the serotoninergic raphe-hippocampus system has been studied in this paper. Topical microinjections of serotonin into the dorsal hippocampus increased morphine analgesia in a dose-dependent fashion, while application into the striatum had no effect. Morphine injections into the median raphe nucleus in relatively low doses exert an antinocifensive effect which is inhibitable by methysergide. Lysergic acid diethylamide administered into the median raphe nucleus also abolished the effect of morphine in a dose-dependent manner. The results in connection with literature data lend support to the presumed integrative function of the serotoninergic raphe-hippocampus system in the mechanism of antinocifensive action of morphine.     

Replacement time for alveolar lipid removed by pulmonary lavage: effects of multiple lavage on lung lipids.

Daily washing in vivo of the lung with 0.15 M saline did not deplete the Beagle dog lung of surfactant lipids, but rather increased the quantity of surfactant lipid in the tissue. Replacement time for the lung lipids removed by the lavage was approximately 5 hours. This rate is one indication of the time required for movement of surfactant lipid from storage areas to the surface of the alveoli. The increase in tissue surfactant lipid following multiple lavage suggests that the rate of surfactant lipid synthesis is controlled in part by the level of surfactant lipid in the alveoli.