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Biomedical subjects

C Lau

Publications and source records attributed to C Lau.

At least 163 records · Page 9Linked to original sources
PubMed1977

Effects of maternal ethanol ingestion on amine uptake into synaptosomes of fetal and neonatal rat brain.

Pregnant rats were kept on an ethanol-containing (6.8% v/v) liquid diet either from the 13th or 18th day of gestation. In pups exposed to ethanol from the 13th day of gestation, synaptosomal uptake of 3H-tyramine and its conversion to 3H-octopamine were increased initially and exposure to ethanol from the 18th day of gestation produced increases in synaptosomal uptake and conversion for longer periods. These changes were not observed in adult rats administered ethanol. Brain tyrosin hydroxylase activity in the developing rats was unaltered by continuous exposure to ethanol. Withdrawal from ethanol either at 0, 3 or 5 days of age enhanced the tendancy toward increased synaptosomal uptake and conversion, but the magnitude of change depended upon the time of exposure and the age at which withdrawal was initiated. These results suggest that maternal ethanol ingestion can affect synaptic function in the developing central noradrenergic system, with consequent alterations in neurotransmitter uptake and storage.

Amines↗
PubMed1976

Proteolytic and chemical modification of colicin E3 activity.

Proteolyses of colicin E3 by both trypsin and subtilisin yield fragments of various molecular weights. On the basis of sodium dodecyl sulfate gel electrophoresis, tryptic cleavage yields peptides of molecular weight about 42 000 and 18 000, while the comparable pieces in a subtilisin digest have apparent weights of about 36 000 and 24 000. The digests lose almost all of their in vivo cell killing activity but the in vitro activity leading to ribosomal inactivation is augmented. Trypsin-treated colicin E3 shows a 20-30-fold increase in its ability to release the 52 nucleotide fragment from the 16S ribosomal ribonucleic acid (rRNA) and this activity is associated with the smaller fragment. Subtilisin-treated colicin E3 is only about two to three fold more active than the native protein in vitro, and the peptides obtained upon cleavage cannot be separated by gel filtration or polyacrylamide gel electrophoresis without sodium dodecyl sulfate. However, in the presence of 0.1% sodium dodecyl sulfate, subtilisin-treated E3 shows a 20-30-fold augmentation in in vitro activity which is again associated with the smaller fragment extracted from the sodium dodecyl sulfate gel. Amino terminal end-group studies showed that the two larger fragments and intact E3 have the same N-terminal residue, valine. These fragments presumably originate from the amino end of the native protein. The smaller tryptic fragment has an N-terminal alanine, while the smaller subtilisin piece has an N-terminal leucine. In addition, modification of a single carbosyl group in intact colicin E3 abolishes more than 90% of the in vivo activity with a simultaneous increase in in vitro activity. This carboxyl group is located in the larger fragments obtained in both trypsin and subtilisin cleavage. Binding of E3 to sensitive cells is drastically reduced or eliniated by this chemical modification and by both of the limited proteolytic cleavages.

Amino Acids↗
PubMed1976

Behavior of colicins E1, E2, and E3 attached to sephadex beads.

Colicins E1, E2, and E3 were covalently attached to Sephadex G-25 beads by cyanogen bromide activation. These immobilized colicins were still active in binding to specific receptors on sensitive and tolerant cells but not to resistant cells which lack such receptors. Bound colicin E3 also retained its ability to inhibit protein synthesis in vitro. Leakage of free colicin from these coated beads was negligible. Assays sensitive to free colicin activity of 1 part in 10(7) of the bound toxin failed to detect any soluble activity. The viability of different cell types bound specifically onto these colicin-Sephadex beads was assayed by using autoradiography based on labeled amino acid uptake. Immobilized E1 killed 90% of bound sensitive cells while less than 10% of sensitive cells bound to E2 and E3 were killed in this assay. These observations agree very well with previously suggested mechanisms which propose that E1, whose target site appears to be at the membrane level, can kill sensitive cells by binding to the cell surface, but that for E2 and E3 penetration of part or all of the molecule is necessary for killing action to be observed.

Binding Sites↗
PubMed1976

Indirect and direct inhibition of dopamine beta-hydroxylase by amphetamine in storage vesicles and synaptosomes.

1 To elucidate the mechanism by which amphetamine produces a functional inhibition of dopamine beta-hydroxylase (DBH), the actions of amphetamine on amine uptake and beta-hydroxylation were examined in isolated adrenal storage vesicles and in whole brain synaptosomes of the rat. 2 Amphetamine produces a competitive inhibition of catecholamine incorporation into adrenal vesicles with a Ki of 279 muM; this action of the drug accounted for slightly less than half of the total inhibition of beta-hydroxylation in the vesicles, indicating that the interference by amphetamine of access of substrate to the enzyme compartment plays an important role in functional inhibition of DBH. The remainder of the effect in vesicles probably represents direct inhibition of the enzyme. 3 In synaptosomes, similar actions on uptake of substrate and on functional enzyme activity were noted, indicating that amphetamine-induced inhibition of the neuronal amine pump can also affect DBH activity if the substrate is supplied exogenously. 4 In addition to the effects of amphetamine in vitro, chronic administration of amphetamine to rats produced an increase in total activity of adrenal DBH. 5 The net effect of amphetamine on DBH activity thus represents the summation of direct inhibition of the enzyme, indirect inhibition via reduced access of substrate and enhancement of activity via trans-synaptic induction.

Adrenal Glands↗
PubMed1976

Effects of neonatal or maternal methadone administration on ornithine decarboxylase activity in brain and heart of developing rats.

Methadone was administered daily to pregnant or nursing rats, or directly to neonates, and the effects on brain and heart weights and ornithine decarboxylase (ODC) activities were determined during postnatal development. Exposure to methadone in the postnatal period either directly or via the mother resulted in delays in maturational decreases in brain ODC accompanied by deficits in brain weight. Prenatal exposure alone had less effect on brain weight or ODC but appeared to enhance the effect of subsequent methadone exposure during the postnatal period. In the heart, direct methadone exposure or prenatal plus postnatal maternal administration led to a pattern of altered ODC activity consistent with delayed development, accompanied by heart weight deficits. The disturbance of heart ODC development after purely prenatal or purely postnatal maternal exposures differed from that obtained after direct administration to the neonate. These data show that exposure to methadone during fetal and/or neonatal life produces alterations in polyamine metabolism which may result in abnormal organ development. The type of change is dependent upon the period and route of exposure and may reflect both direct effects on the pup and indirect effect from drug-induced alterations in maternal metabolism or behavior.

Aging↗