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Biomedical subjects

G B Brown

Publications and source records attributed to G B Brown.

At least 55 records · Page 3Linked to original sources
PubMed1981

Interaction of batrachotoxinin-A benzoate with voltage-sensitive sodium channels: the effects of pH.

The binding of labeled batrachotoxinin-A benzoate (BTX-B) to voltage-sensitive sodium channels in broken membrane preparations of mouse cerebral cortex has been measured as a function of the pH. Specific binding is negligible at pH less than 6.0, maximum at pH 8.5, and decreases again at pH 9.0. A major component of nonspecific binding, however, increases linearly in the pH range 7.0-9.0. The pKa of batrachotoxinin-A, an analogue of BTX-B, was found by titrimetric methods to be greater than or equal to 8.2. Analysis of the data shows that at least part of the pH dependence of BTX-B binding is due to the titration of a sodium channel residue(s) associated in some way with the BTX-B recognition site. The possible involvement of a histidine residue is suggested.

Animals↗
PubMed1981

Batrachotoxinin-A 20-alpha-benzoate: a new radioactive ligand for voltage sensitive sodium channels.

Batrachotoxinin-A 20-alpha-benzoate (BTX-B), an analog of the potent depolarizing agent batrachotoxin (BTX), was prepared by selective esterification of naturally occurring batrachotoxin-A with benzoic acid. BTX-B depolarized rat phrenic nerve-diaphragm preparations with a time course and concentration dependence virtually indistinguishable from that of BTX. A specific, saturable component of equilibrium binding of [3H]BTX-B to mouse cerebral cortex homogenates was measured, described by an equilibrium dissociation constant of 0.7 microM and a maximum number of binding sites of 90 pmol per gram of tissue (wet weight). Specific binding is inhibited by BTX and other BTX analogs, veratridine, and grayanotoxin but is unaffected by tetrodotoxin and cevine. Under conditions of this assay, neither crude Leiurus quinquestriatus scorpion venom nor purified sea anemone toxin have any effect of specific binding. The data support the conclusion that BTX-B interacts with a recognition site associated with voltage sensitive sodium channels which is identical to the recognition site for BTX.

Animals↗
PubMed1978

Oncogenicity of purine 3-oxide and unsubstituted purine in rats.

Injection s.c. of purine 3-oxide into Wistar rats resulted in the appearance of sarcomas and fibromas at the interscapular site of administration, carcinomas in the liver, and a high incidence of s.c. fibromas in the hip at a distance from the site of injection. A small number of liver tumors but not tumors at the injection site appeared in rats to which the parent compound, purine, was administered. Oxidation of purine 3-oxide by xanthine oxidase was found to occur in two steps to yield the potent oncogen 3-hydroxyxanthine. A similar process may occur in vivo since a protein preparation from rat s.c. tissue has similar oxidizing activity.

Animals↗
PubMed1978

3-Hydroxyxanthine: transplacental effects and ontogeny of related sulfate metabolism in rats and mice.

The ontogeny of sulfate metabolism related to the metabolic activation of the carcinogenic purine N-oxide 3-hydroxyxanthine (3-OH-X) was studied in noninbred Sprague-Dawley rats. Sulfotransferase activity toward 3-OH-X was detectable in most fetal livers near term at about 25% of adult values and increased slowly after birth. This activity was also present in placentas. Compared to 3-OH-X sulfotransferase, sulfotransferase activity toward p-nitrophenol was lower in fetal livers and was not detected in placentas. Sulfohydrolase activity toward 3'-phosphoadenosine-5'-phosphosulfate was higher in fetal and newborn livers and in placentas than in adult liver. In a parallel transplacential carcinogenicity assay, a low but significant percentage of male rats exposed as fetuses to multiple high doses of 3-OH-X developed single liver carcinomas. After the lowest transplacental dose, the incidence of degenerative kidney disease in old male offspring was significantly higher than that in controls. In an assay with mice, (C57BL/6 X BALB/c)F1 mice exposed transplacentally to 3-OH-X experienced significantly greater perinatal morality and fewer lung adenomas among the surviviors at 20 months of age than did the controls.

Animals↗
PubMed1978

Increased incidence of mammary tumors in rats after direct or transplacental exposure to 3-hydroxyxanthine.

Rats were exposed directly or transplacentally to the carcinogenic purine N-oxide 3-hydroxyxanthine (3-OH-X). Among female noninbred Wistar rats given 3-OH-X sc, beginning at suckling or weaning ages, there was a significantly greater proportion of mammary tumor bearers and a higher mean number of mammary tumors per rat than among controls. This effect was seen even at low doses producing no other neoplasms such as hepatic carcinomas or fibrosarcomas and fibromas at the site of injection. Noninbred Sprague-Dawley rats, treated transplacentally with 3-OH-X by ip injection into pregnant females, also also had a significantly greater incidence of mammary tumors than did controls.

Age Factors↗
PubMed1977

Methylation of intestinal and hepatic DNA in rats treated with methylazoxymethanol acetate.

Descending colon is the most sensitive segment of rat intestine and is at least as sensitive as liver to the carcinogenic effects of methylazoxymethanol acetate. To determine whether a relationship exists between tumor induction and level of DNA methylation, we measured the levels of 7-methylguanine in the DNA isolated from duodenum, descending colon, and liver of rats treated with this carcinogen. Because radiolabeled methylazoxymethanol acetate is not available, we utilized high pressure liquid chromatography whereby methylated purines could be detected in amounts as little as 100-300 pmoles. DNA isolated from liver of carcinogen-treated rats had significant amounts of 7-methylguanine. On the contrary, DNA isolated from descending colon of rats treated with methylazoxymethanol acetate had minimal amounts of 7-methylguanine; these data suggest that the level of 7-methylguanine does not correlate with sensitivity to tumor induction by methylazoxymethanol acetate.

Animals↗
PubMed1977

Evidence that nystatin may not form channels in thin lipid membranes.

The mechanism of nystatin-induced conductance increases in planar bilayer membranes formed from lecithin/cholesterol (1:1) has been examined by spectral analysis of kinetic fluctuations. Lorentzian components of the power spectrum, characteristic of channel activity, were not observed for nystatin-doped membranes. Instead, the noise associated with this system (approximately 10(-27)A2/Hz) was in better agreement with that expected of a carrier mechanism involved in the transport of single charges in uncorrelated fashion. The implications of this result with respect to previous models of nystatin-induced conductance increases are discussed.

Alamethicin↗