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O M Rennert

Publications and source records attributed to O M Rennert.

At least 55 records · Page 3Linked to original sources
PubMed1987

Absence of a 23 kd protein in testes of testicular feminization rat.

Cryptorchid testes of testicular feminization rats are very low in zinc in spite of normal zinc status of the animals. Analysis of the cytosol of the cryptorchid testes by gel permeation chromatography showed decreased zinc binding by proteins eluted at fractions corresponding to 30,000 dalton. Further analysis by sodium dodecylsulphate polyacrylamide gel electrophoresis indicated the absence of a protein with molecular weight of 23,000.

Androgen-Insensitivity Syndrome↗
PubMed1987

Coincidence of seizure susceptibility to caffeine and to the benzodiazepine inverse agonist, DMCM, in SWR and CBA inbred mice.

Several lines of evidence suggest that the convulsant actions of caffeine are mediated through benzodiazepine receptors. A pharmacogenetic approach has been used to further explore the relationship of these receptors to caffeine-induced seizures. The susceptibility of two inbred strains of mice (CBA and SWR) to the convulsant actions of picrotoxinin, strychnine, Ro 5-4864 and DMCM was examined. Previous studies have demonstrated these two strains differ in their susceptibilities to the convulsant action of caffeine. While no differences were observed between these two strains in susceptibility to tonic seizures induced by picrotoxinin, RO 5-4864 or strychnine, SWR mice were significantly less sensitive to tonic seizures induced by DMCM compared to CBA mice (CD50 values in CBA and SWR mice were 6 and 12 mg/kg IP). Both clonazepam and the benzodiazepine receptor antagonist, Ro 15-1788, significantly blocked caffeine-induced seizures. Further, when subconvulsant doses of caffeine and DMCM were combined, a synergistic action was observed. Taken together, these findings support the hypothesis that the convulsant actions of caffeine result from an action at benzodiazepine receptors, and that the hyporesponsiveness of the SWR strain to both caffeine- and DMCM-induced seizures could result from an inherited abnormality in these sites.

Animals↗
PubMed1987

Different genes specify hyporesponsiveness to seizures induced by caffeine and the benzodiazepine inverse agonist, DMCM.

Two strains of inbred mice differed significantly in their susceptibility to tonic seizures induced by caffeine and the benzodiazepine inverse agonist, methyl 6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate (DMCM). The hyporesponsive strain, SWR, was not less susceptible to the convulsant action of other chemical convulsants, an observation which indicated that the response differences between the strains were pharmacologically specific. These observations and drug interaction studies suggested that caffeine-induced seizures might be mediated through an "inverse" agonist-like action of caffeine on benzodiazepine receptors associated with GABA receptor-benzodiazepine receptor-chloride ionophore complex. To determine whether the coincident alteration in susceptibility to DMCM and caffeine resulted from a single mutational change or was the result of two different genetic changes occurring coincidentally between these two strains of mice, progeny from conventional Mendelian crosses (F1, F2 and reciprocal backcrosses) were analyzed for the co-segregation of susceptibility to DMCM and caffeine. The inheritance of DMCM sensitivity was consistent with a single autosomal gene determinant in which the allele specifying increased responsiveness was dominant to the allele determining hyporesponsiveness. The frequent occurrence of recombinant phenotypes (e.g., caffeine hyporesponsive but DMCM sensitive mice) among F2 and backcross progeny established that different genetic determinants encode DMCM susceptibility and caffeine susceptibility in these two strains of mice. Thus, while these data establish a simply inherited difference in benzodiazepine responsiveness between the two mouse strains, they also indicate that this pair of strains is inappropriate for a genetic analysis aimed at probing the relationship between caffeine-induced seizures and the benzodiazepine receptor.

Animals↗
PubMed1986

Androgen receptors in ventral prostate glands of zinc deficient rats.

Androgen binding has been studied in the prostate cytosol of zinc deficient rats by charcoal assays. Rats were housed individually in plastic cages and maintained on a zinc deficient diet for 3 months. The cytosol fraction of prostate gland was incubated with various concentrations of tritiated methyltrienolone (3H-R1881, a synthetic androgen) alone or in the presence of 500-fold excess of radioinert R1881. Scatchard analysis of the data revealed that the number of androgen binding sites in the cytosol fraction of the zinc deficient rat prostate was 31 +/- 5.2 fmol/mg cytosol protein. This was significantly lower than that (84 +/- 11.5 fmol/mg protein) of the controls. Their dissociation constant (Kd = 1.6 +/- 0.6 nM) on the other hand was not different from that (1.7 +/- 0.7 nM) of control animals. This decrease in the concentration of cytosol receptor sites in the zinc deficient state suggests that this metal is involved in the androgen-binding process in the target cells.

Androstane-3,17-diol↗
PubMed1986

Inherent hyporesponsiveness to methylxanthine-induced behavioral changes associated with supersensitivity to 5'-N-ethylcarboxamidoadenosine (NECA).

Two inbred mouse strains, SWR and CBA, differed significantly in their susceptibility to acute dose dependent theophylline- and caffeine-induced stimulation of locomotor activity. The efficacy of both methylxanthines was reduced in the SWR strain compared to the CBA strain. When brain levels of theophylline were determined at a dose (32 mg/kg IP) which gave maximal behavioral separation of the two strains, no significant differences were found between them (SWR levels 12.5 +/- 1.9, CBA levels 14.3 +/- 1.7 micrograms/g wet weight brain). The dose dependent ability of several adenosine agonists (N6-cyclohexyladenosine, (-)-N6-phenylisopropyladenosine, 5'-N-ethylcarboxamidoadenosine) to depress locomotor activity was investigated. SWR mice were found to be significantly more sensitive to NECA-induced depression of locomotor activity and the NECA-induced hypothermia than were CBA mice (respective ED50 values for inhibition of activity, 11.6 and 30.5 nmoles/kg IP). No differences were found in brain [3H]-NECA levels at doses which produced marked differences in behavioral effects between the two strains. The differences in adenosine agonist sensitivity between the strains were both agonist- and behavior-specific. These data indicate that an inherited alteration in behavioral responsiveness to methylxanthine administration can be inversely associated with inherent alterations in susceptibility to the action of specific adenosine analogs. An adenosine A-2 receptor sub-class may be involved in these changes in in vivo pharmacological susceptibility to the action of both methylxanthines and adenosine agonists on locomotor activity.

Adenosine↗
PubMed1986

Complex genetic determinants of susceptibility to methylxanthine-induced locomotor activity changes.

The intent of this study was to investigate the role of inheritance in the determination of susceptibility to methylxanthine-induced behavioral changes. Two strains of inbred mice, SWR and CBA, which differ significantly in their response to caffeine- and theophylline-induced stimulation of locomotor activity, were used in classical genetic crosses to produce reciprocal F1 hybrids, reciprocal backcross progeny F2 progeny. Theophylline dose response curves in the reciprocal F1 hybrid strains were identical to each other and to their methylxanthine-responsive (CBA) parent. These results indicated that theophylline responsiveness behaved as a simple autosomal dominant trait. Behavioral responses of these F1 hybrid strains to caffeine showed the same maximal enhancement of locomotor activity as their CBA progenitor at a dose 10 mg/kg IP, but locomotor activity stimulation also occurred at 32 mg/kg IP, a dose which inhibited their CBA parent. These data suggest that the genes specifying caffeine responsiveness differ from those encoding theophylline responsiveness. For both caffeine and theophylline, behavioral phenotypes and their expected frequencies of occurrence among backcross and F2 progeny differed significantly from the segregation ratios expected for a trait determined by a single gene. These non-Mendelian segregation ratios suggest that locomotor activity stimulation by both of these methylxanthines is polygenically determined. It was anticipated that the same genetically encoded neurochemical mechanism would underlie the difference in behavioral response to the two methylxanthines. However, no significant correlation between caffeine-induced and theophylline-induced stimulation of locomotor activity was observed among progeny derived from backcrosses of F1 self-crosses.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Differential antagonism of the behavioral depressant and hypothermic effects of 5'-(N-ethylcarboxamide) adenosine by theobromine.

The methylxanthine, theobromine (3,7-dimethylxanthine), was tested in mice, to determine whether theobromine could function in vivo as an adenosine receptor antagonist, in keeping with its reported in vitro effects as a blocker of agonist binding to the adenosine A-1 receptor. Theobromine doses, which themselves had no direct effects on spontaneous locomotor activity, completely blocked N6-cyclohexyladenosine-induced suppression of locomotor activity but were without effect on 5'-N-ethylcarboxamide adenosine (NECA)-induced decreases in motor activity. In contrast to the specific antagonism, theobromine blocked the hypothermia induced by both of these adenosine analogs. These results demonstrate that theobromine is an active in vivo adenosine receptor antagonist and that the antagonism of N6-cyclohexyladenosine sensitive systems occurs even though theobromine does not stimulate spontaneous locomotor activity. Thus, the behavioral stimulant effects of methylxanthines may be more related to effects on NECA-sensitive systems, which are not blocked by theobromine. The use of in vivo differences in the effects xanthine may provide a useful tool in the development of compounds to probe the mechanisms of caffeine induced CNS effects.

Adenosine↗
PubMed1986

Comparative biological availability of manganese from extrinsically labelled milk diets using sucking rats as a model.

1. Very little is known about the biological availability of manganese from human milk and other infant milk diets. To determine the relative Mn availability, and to examine whether the age and the duration of previous fasting affect Mn absorption, sucking rats were given human milk, bovine milk and infant formula (regular Similac; Ross Laboratories, Columbus, OH) extrinsically labelled with 54Mn. 2. Milk diets were given by gastric intubation and the radioactivity of the carcass, liver and digestive tract was measured 3 h after feeding. 3. The concentration of endogenous Mn was lowest in human milk (7-10 micrograms/l) and highest in rat milk (140-165 micrograms/l). Increasing the non-radioactive total Mn concentrations of either human milk or bovine milk up to 150 micrograms/l did not affect the absorption of 54Mn by 10-d-old rats. 4. No significant (P greater than 0.05) difference in 54Mn absorption was found among the three milk diets (human milk, bovine milk, infant formula) in 8- to 11-d-old rats. However, significantly more (P less than 0.05) 54Mn was absorbed from human milk and infant formula than from bovine milk when 13-d-old rats were used. 5. 54Mn radioactivity detected in carcasses of 8-, 9-, 10- and 11-d-old rats ranged from 25 to 27% of the dose from various milk diets. The activities of 54Mn in the carcasses of 13-d-old rats were 15, 11, and 16% of the dose from human milk, bovine milk and infant formula respectively. 6. The trend of 54Mn incorporation into liver was similar to that of the carcass and over 60% of the absorbed 54Mn was incorporated into the liver regardless of the type of milk used. 7. Absorption of 54Mn from extrinsically labelled rat milk using 9- or 10-d-old sucking rats was similar to its absorption from infant formula. 8. The absorption of 54Mn from the three milk diets decreased with age of the neonatal rats and 54Mn absorption from human milk, bovine milk, infant formula as well as rat milk was affected similarly by duration of previous fasting.

Animals↗
PubMed1986

Comparative studies of selenium-75 (selenite and selenomethionine) absorption from various milk diets in suckling rats.

Selenium (Se) absorption was studied in human milk, bovine milk and infant formula (Similac) using suckling rats as a model. The effect of age on Se absorption from the three milk diets extrinsically labeled with 75Se, either as selenite or selenomethionine, was also investigated. Milk diets were fed by gastric intubation and the radioactivity in the carcass, gastrointestinal tract and the liver were measured 3 h after feeding. There was no difference in [75Se]selenite absorption from the three milk diets between 8-20 d of age. However, significantly higher quantity of 75Se was absorbed from all three milk diets by 20-d-old rats than by the younger rats (46 vs. 32%). This increase in [75Se]selenite absorption with advancing age is opposite to what has been found for most other trace elements. When rats were fed milk diets labeled with [75Se]selenomethionine, the absorption of 75Se was approximately twofold higher in all age groups compared with 75Se absorption from selenite. No difference in [75Se]selenomethionine absorption existed among the three milk diets in 8- or 10-d-old suckling rats. However, at 15 d of age [75Se]selenomethionine absorption from human milk was higher (82%) than from either bovine milk (72%) or infant formula (72%). Between 8 and 20 d of age, absorption of [75Se]selenomethionine from the three milk diets decreased with advancing age. Adding sodium selenate to increase the total nonradioactive Se of human milk, bovine milk (endogenous plus the added selenium) did not affect the absorption of either [75Se]selenomethionine or [75Se]selenite.

Aging↗
PubMed1986

Abnormal zinc metabolism in unilateral maldescended testes of a mutant rat strain.

The status of zinc in a mutant rat strain with heritable maldescended testes was examined. In rats with unilateral maldescended testis, the ectopic testis consistently had decreased zinc content (121.0 +/- 23.0 micrograms zinc/g dry wt), while the eutopic testis had zinc content similar to that of normal rats (182.0 +/- 5.0 micrograms zinc/g dry wt). Uptake of zinc by the ectopic testis was comparable to normal. Sephadex gel chromatography showed greatly reduced zinc content of one of the endogenous zinc binding fractions with a mol wt of 30,000 of cytosol of the ectopic testis in spite of a near normal protein content. Incorporation of zinc-65 into this fraction was also shown to be greatly reduced in ectopic testis. Sodium dodecylsulphate-polyacrylamide gel electrophoresis demonstrated that a protein of 23,000 Da was greatly reduced in quantity. This 23-kDa protein in ectopic testis may play a role in reduced testicular function of the ectopic testis.

Animals↗
PubMed1985

Glucose tolerance and plasma lipid distributions in rats fed a high-sucrose, high-cholesterol, low-chromium diet.

Male Sprague-Dawley rats were fed either a low-chromium (60 to 100 micrograms per kg of diet) or chromium-supplemented (5 mg per kg of diet), high-sucrose, high-cholesterol diet from weaning until age 18 months. Rats that were pair- and meal-fed the low-chromium diet had higher one-hour postprandial plasma glucose concentrations than their supplemented partners at ages 4 and 8 months (P less than 0.05), but not at age 12 months. One-hour postgavage (250 mg glucose/100 g body wt) glucose concentrations did not differ between dietary groups at 12 months. Plasma cholesterol concentrations increased up to age 12 months, but neither they nor postprandial triglyceride concentrations differed significantly between dietary groups. Ad libitum feeding of the low-chromium and chromium-supplemented diets was initiated at age 14 months in order to determine whether there were differences due to dietary chromium content which might not be manifest on the pair-feeding regimen. Animals of both dietary groups had significant weight gain by age 16 months, but their one-hour postgavage plasma glucose concentrations did not differ significantly. Plasma cholesterol concentrations increased significantly following institution of ad libitum feedings, but neither they nor lipoprotein cholesterol or triglyceride distributions differed significantly between dietary groups. Experimental conditions, methods, and results from this study and previous studies are compared and critically examined. We suggest that other factors in addition to dietary chromium content may contribute to the differences in glucose tolerance and plasma cholesterol concentrations described in such studies and that there is a need for improved documentation of glucose intolerance and tissue chromium concentrations in this animal model.

Animals↗
PubMed1985

Inheritance of amphetamine-induced thermoregulatory responses in inbred mice.

Two inbred strains of mice, DBA/2 and C57BL/6, differ in their responses to d-amphetamine-induced alteration of core temperature. At low doses of amphetamine (e.g., 2 mg/kg IP), both strains become markedly hypothermic within 10-20 minutes. High doses (e.g., 20 mg/kg IP) induce significant hyperthermia (+1.8 degrees C) in DBA/2 mice but have only a slight hyperthermic effect (+0.2-0.3 degrees C) effect on C57BL/6 mice. The phenotype of the F1 hybrid strain derived by crossing C57BL/6 by DBA/2 is indistinguishable from its C57BL/6 parent at a dose of 20 mg/kg IP, i.e., reduced responsiveness to amphetamine-induced hyperthermia is dominant. Analysis of the thermoregulatory responses of recombinant inbred derivatives (lines BXD-9, 11, 15, 19, 20, 21, 23, 27, 28, 30) suggest that the relative responses to amphetamine-induced hyperthermia is inherited in a simple Mendelian fashion. These results differ from other pairs of inbred mouse strains which have been compared. These findings identify yet another neuropharmacological difference between mouse strains C57BL/6 and DBA/2 and are reviewed in terms of neuroregulatory mechanisms effecting thermoregulation.

Amphetamine↗
PubMed1985

A single gene difference determines relative susceptibility to caffeine-induced lethality in SWR and CBA inbred mice.

Inbred mouse strains SWR and CBA differ markedly in their relatively susceptibility to the acute toxic effects of intraperitoneally administered caffeine. At a dose of 187 mg/kg, SWR mice survive a stress-potentiated lethality test apparently related to the generation of tonic seizures; in contrast, CBA mice usually die in less than 30 seconds after this dose. Progeny from several different genetic crosses were characterized to determine the genetic basis underlying this phenotypic difference in caffeine sensitivity. F1 progeny from reciprocal crosses of the parental strains were uniformly sensitive to caffeine-induced lethality, i.e., caffeine responsiveness behaves like an autosomal dominant trait. Self-crossing of F1 individuals produced both progeny which were resistant to caffeine-induced lethality (26% of the total) and those which were susceptible (74%). Backcrosses of the F1 animals to the CBA parent produced no (0/19) resistant progeny. In contrast, backcrosses of F1 animals to SWR produced 54% resistant progeny. These data indicate that the difference in susceptibility to caffeine-induced lethality between these strains is determined by a single pair of autosomal alleles in which susceptibility (responsiveness) to this methylxanthine is dominant to resistance (nonresponsiveness).

Animals↗
PubMed1985

Genetic trace metal disturbances.

Genetic trace metal disturbances can be at three levels. Trace metals play an important role in the metabolism of genetic macromolecules and the information transfer system. Deficiency or excess of trace metals caused either by dietary or genetic factors will affect the normal functioning of the whole organism. The roles of trace metals in carcinogenesis/mutagenesis and ageing are typical of this category. The second level of genetic trace metal disturbances affect the metabolic pathway of the trace metal itself. Biochemical derangement resulting from genetic defects cause aberrant metabolism of the element and thus disease symptoms. Diseases caused by abnormal metabolism of copper, zinc, iron, and molybdenum are discussed. Trace metal disturbances can also be the result of other genetic diseases. This aspect of genetic trace metal disturbances is least investigated. However, information should be important for improving the existing treatment protocol for the more common inborn errors of metabolism, such as phenylketonuria.

Animals↗
PubMed1985

Zinc deficiency acts as a co-teratogen with alcohol in fetal alcohol syndrome.

Because alcoholism has adverse effects on zinc nutrition and many pregnant women consume less than the recommended dietary allowances of zinc, we postulated that zinc deficiency acts as a co-teratogen with alcohol in the fetal alcohol syndrome. We compared the effects of alcohol on progeny of pregnant mice fed a zinc-deficient diet compared to those fed a diet with adequate zinc. Pregnant CBA mice (n = 66) were fed the Lieber-DeCarli liquid diet with 0, 15, or 20% ethanol-derived calories containing 0.3 (low) or 8.5 (high) micrograms zinc/ml. Dams were sacrificed on day 18 of gestation. Resorptions, malformations, and individual fetal weights were recorded. Analysis of fetuses included assays for zinc, assessment of soft tissue malformations, and alizarin red staining for skeletal malformations. Fetal weights were lower in the groups fed the zinc-deficient diet for each concentration of alcohol (p less than 0.005). The groups fed the combination of low zinc plus alcohol had 37-52% resorptions, while the animals on the zinc-deficient diet without alcohol or the high zinc diet with alcohol had 0-2% resorptions. Skeletal malformations were related to alcohol concentration but not zinc intake, while external malformations were higher in those maintained on the low zinc-ethanol diet. These results suggest that zinc deficiency potentiated the teratogenic effects of alcohol and that nutritional intervention for alcoholic women during pregnancy might reduce the incidence or severity of fetal alcohol syndrome.

Abnormalities, Multiple↗
PubMed1984

Intestinal transport of manganese from human milk, bovine milk and infant formula in rats.

The transport of manganese from extrinsically labeled human milk, bovine milk and infant formula was studied by the everted intestinal sac method. Tissue/mucosal flux data indicated that transport of manganese into the intestinal tissue was significantly greater with bovine milk and formula than from human milk. Similarly, the total flux of manganese from the mucosal to serosal surface was less when human milk was used. Smaller molecular weight manganese binding ligands isolated from the milk samples enhanced the mucosal to tissue movement of manganese as contrasted to the higher molecular weight manganese binding ligands. Most significantly the data suggest that the transport and uptake of manganese is less in the presence of human milk and its isolated manganese fractions than it is in bovine milk or infant formula.

Animals↗
PubMed1984

Systematic comparison of apomorphine-induced behavioral changes in two mouse strains with inherited differences in brain dopamine receptors.

Dosage and time dependencies of apomorphine-induced changes in stereotyped behaviors (climbing, gnawing and sniffing), locomotor activity and rearing activity were compared in young adult male mice of two inbred strains, DBA/2 and C57BL/6. These two strains are known to differ in their genetically specified brain dopamine receptor number. Apomorphine administered intraperitoneally at dosages of 0.5-20 mg/kg failed to induced stereotyped climbing in DBA/2 at any of the doses tested but markedly increased climbing in C57BL/6 at higher dosages. Apomorphine-induced stereotyped gnawing occurred in both strains at higher dosages although the latency was shorter and maximal effect greater in C57BL/6. Stereotyped sniffing was induced in both strains to a comparable degree at doses greater than or equal to 2.0 mg/kg, and the duration of this stereotypy was indistinguishable between strains. Locomotor activity was inhibited maximally in DBA/2 at an apomorphine dosage of 2 mg/kg and was inhibited to a greater extent than was C57BL/6. Rearing was inhibited in both strains by doses of apomorphine greater than or equal to 0.5 mg/kg; however the duration of the effect was considerably greater in DBA/2 than in C57BL/6. These data suggest that genetically determined differences in central dopamine receptors may have profound and selective effects on behaviors mediated by dopamine pathways; that complex behavioral patterns, e.g., apomorphine-induced stereotypy, may be dissected in to individual components by identifying neuropharmaco genetic differences between strains; that marked strain-specific, inherited differences in dopamine agonist-induced behavioral changes do occur among inbred, non-mutant mouse strains and that their occurrence in other mammalian species including man should be considered.

Animals↗