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Biomedical subjects

G M Anderson

Publications and source records attributed to G M Anderson.

8 recordsLinked to original sources
PubMed1992

Differentiation of Neuro-2a neuroblastoma cells by an antibody to GM3 ganglioside.

A monoclonal antibody against GM3 ganglioside (GM3Ab) was found to trigger differentiation of Neuro-2a cells in culture. The differentiation of Neuro-2a cells by GM3Ab was accompanied by increased levels of intracellular serotonin and amino acid neurotransmitters viz. aspartate, glutamate, glutamine, glycine and taurine. Further study indicated that the increase in the serotonin level was not due to a higher rate of serotonin synthesis but rather to a higher rate of active transport of serotonin from the medium. Studies on the cell surface gangliosides revealed that unlike the proliferating cells, the GM3Ab-mediated differentiated cells contained higher gangliosides in addition to GM3 and GM2 gangliosides. Analysis of total cellular proteins indicated the appearance of a 25 kDa protein, pI 5.4, in the GM3Ab-treated cells--a small amount of this protein was observed in dibutyryl cAMP (Bt2cAMP)-treated cells, however, the protein was totally absent in the 5-bromo-2'-deoxyuridine (BrdU)-treated cells. Investigation of the mode of action of GM3Ab indicated that the cellular differentiation was due to increased cAMP accumulation resulting from an increase in the adenylate cyclase activity. Further studies with different agents affecting protein kinase C (PKC) activity and direct assay of PKC ruled out the possibility that GM3Ab mediated its effect via PKC. This GM3Ab-induced differentiation could be inhibited by protein kinase A (PKA) inhibitor, H8, but could not be inhibited by sphingosine, an inhibitor of PKC. Pertussis toxin could mimic the effect of GM3Ab, suggesting that GM3Ab caused the elevation in the adenylate cyclase activity by reducing the Gi-protein inhibition of the adenylate cyclase. The data suggests that GM3Ab, after interaction with cell surface GM3, elevated intracellular cAMP level by withdrawing the inhibitory effect of some undefined factor(s) present in culture medium which normally keeps adenylate cyclase activity low through activation of Gi-protein.

Amino Acids↗
PubMed1978

Quantitative structure-activity relationships in the 2,4,5-ring substituted phenylisopropylamines.

The potency of a series of 2,4,5-ring substituted phenylisopropylamines was examined using the rabbit hyperthermia assay. An excellent correlation (r = 0.99) was found between the rabbit hyperthermic and human psychotomimetic potencies. In the hyperthermic model, the 4-X-substituted-2,5-dimethoxyphenylisopropylamines were found to be one to two orders of magnitude more potent than the 2-X- or 5-X-substituted positional isomers (X = -H, -CH3, -SCH3, -Br). Conformational perturbations induced by substituents ortho to the ethylamine side chain were studied with the PCILO and ab initio molecular orbital methods. The variations in the biological activities could not be rationalized in terms of the ability of the ortho substituents to stabilize conformations which mimic LSD. The electronic structures of the positional isomers were examined in the corresponding toluene analogues using the CNDO/2 method. A reasonable correlation (r = 0.98) was found between the Highest Occupied Molecular Orbital (HOMO) energy and the ionization potentials reported from photoelectron spectroscopy studies. In the case of the positional isomers, the HOMO energies were ordered as follows: 4-X greater than 5-X greater than 2-X. However, the regression analysis of the relationship between these orbital energies and Log Biological Activity (B.A.) was not impressive. Examination of the partition coefficients (octanol/water) of the positional isomers indicated that the 4-X- and 5-X-substituted compounds have almost equivalent Log P's, but that the 2-X-substituted-4,5-dimethoxyphenylisopropylamines are unusually hydrophilic. The regression of Log H.P. to the HOMO energies resulted in a marginally significant relationship; addition of the Log P's resulted in no significant improvement. Qualitative models based on both regiospecific lipophilicity or electron densities and also metabolic conversion to reactive intermediates are presented.

Animals↗
PubMed1975

Quantitation of tryptophan metabolites in rat feces by thin-layer chromatography.

Indole, skatole, indole-3-acetic acid, indole-3-propionic acid, tryptamine, and free tryptophan have been extracted from rat fecal samples and quantitated by thin-layer chromatography. Additional tryptophan metabolites have been recovered in yields of 87-97% from supplemented fecal samples. Detection limits for all the compounds studied were in the 0.1 mug/g feces range. Quantitation was possible in the mug/g range with an estimated accuracy of plus or minus 10%.

Animals↗
PubMed1975

Formation of indoleacetic acid by intestinal anaerobes.

Indoleacetic acid was produced from tryptophan by only three of 23 intestinal anaerobes studied. Evidence is presented to show that the formation of indoleacetic acid proceeds through the intermediate, indolepyruvic acid, via transamination with alpha-ketoglutarate rather than by tryptamine pathway.

Anaerobiosis↗