Elevation of nerve growth factor receptor-truncated in the urine of patients with diabetic neuropathy.
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Adult↗
Biomedical subjects
R E Hruska
Publications and source records attributed to R E Hruska.
Immunoassay reagents for psychoactive drugs. Part 3. Removal of phenothiazine interferences in the quantification of tricyclic antidepressants.
Phenothiazines and their metabolites are known to interfere in the quantification of tricyclic antidepressants (TCAs). A method for selective chemical modification of phenothiazines by chloramine-T in the presence of TCAs is described. This method allows for accurate quantification of the TCA analyte in a serum sample without interference from the modified phenothiazine.
Antidepressive Agents, Tricyclic↗
Species differences in estrogen receptors and in the response to 2,3,7,8-tetrachlorodibenzo-p-dioxin exposure.
The acute toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exhibits marked interspecies variability, with the guinea-pig, rat and hamster representing the species most sensitive, intermediate and most resistant to acute toxicity. Prepubertal guinea-pigs, rats and hamsters were treated with a single intraperitoneal injection of TCDD in olive oil at doses of 4, 50 and 1500 micrograms/kg, respectively. These exposures were chosen to produce acute toxicity and all 3 species exhibited a decrease in the rate of body weight gain during the 7 days following TCDD exposure when compared with control (olive oil-treated) animals. On the 7th day after exposure, the density and affinity of 17 beta-estradiol receptors were determined in the uterus and liver of TCDD-treated and control animals. The treatment with TCDD did not alter the affinity of the receptors in these 3 species. The density of hepatic 17 beta-estradiol receptors was decreased 65% in the guinea pig and 92% in the rat following exposure to TCDD. In contrast, TCDD-treated hamsters exhibited no change in the density of hepatic 17 beta-estradiol receptors. The uterine 17 beta-estradiol receptors were increased in density by TCDD treatment in the hamster and in the rat when expressed per mg protein. Uterine wet weights in the guinea-pig and rat were also significantly decreased by TCDD treatment but were not changed in the hamster. When the Bmax for uterine 17 beta-estradiol receptors was expressed as pmol/g tissue wet weight. TCDD exposure was found to produce an 11% decrease in density in the rat, while producing a 44% increase in the hamster. In control animals, the density of uterine 17 beta-estradiol receptors correlated inversely with the lethal dose of TCDD in these 3 species (i.e., the guinea-pig has the lowest LD50 and highest density of uterine 17 beta-estradiol receptors). The different responses to TCDD in the 3 species suggest that the changes in 17 beta-estradiol receptors may be related to species-specific toxic responses associated with TCDD exposure.
Animals↗
Kainic acid lesions decrease striatal dopamine receptors and 1,4-dihydropyridine sites.
The effects of intrastriatal injection of kainic acid (2 microliters, 1 mg/ml) in the rat were determined. Four weeks after the lesioning, striatal dopamine receptors and 1,4-dihydropyridine sites were measured by radioligand binding with [3H]spiperone and [3H]nimodipine, respectively. Dopamine receptor and 1,4-dihydropyridine binding densities were decreased by 58% and 43% respectively, with no change in binding affinity for either ligand. 1,4-Dihydropyridine-sensitive Ca2+ channels may be located primarily on postsynaptic elements.
Animals↗
Estrogen treatment increases the density of D1 dopamine receptors in the rat striatum.
Adult, male rats were treated with 17 beta-estradiol valerate by s.c. injection of 125 micrograms/rat. Six days later the density and affinity of striatal D1 dopamine (DA) receptors were determined. Estrogen treatment significantly increased the density of D1 DA receptors without altering their affinity. In vitro co-incubation with 17 beta-estradiol 17 beta-estradiol valerate at concentrations up to 1.0 microM did not alter binding to D1 DA receptors.
Animals↗
Effect of ethanol administration of striatal D1 and D2 dopamine receptors.
Chronic in vivo exposure of rats to ethanol in a complete liquid diet for 14 or 21 days produced a behavioral tolerance to the acute injection of ethanol. After 21 days, but not 14 days, of chronic exposure, there was a significant increase in the maximum density of striatal D1 and D2 dopamine receptors without a change in these receptors' affinities. A 24-h withdrawal from the 21-day exposure did not alter the observed increase in density. Both the level and duration of ethanol exposure appear to be important variables for demonstration of an increase in striatal D1 and D2 dopamine receptors.
Animals↗
Influence of hypophysectomy on dopamine receptors and dopaminergic behaviors.
Hypophysectomy (Hypox) has been proposed to alter the behavioral and biochemical indices of striatal dopamine (DA) function. Since the regulation of striatal DA receptors by hormones may involve the pituitary, it was relevant to reevaluate the effects of Hypox in male and female rats. Behaviorally, dopaminergic agonists exerted enhanced activity in Hypox male and female rats. It has been suggested that these changes are due to altered metabolism since no increase in the DA receptor populations was observed. Dopaminergic antagonists showed equivalent behavioral actions in male and female rats, whether intact or Hypox. Biochemically, neither the density nor the affinity of the striatal DA receptors is altered by Hypox in female rats for 1-2 weeks or male rats for 5-6 weeks. However, in female rats at 5-6 weeks after Hypox there is a significant decrease in receptor number. This decrease in density is not reflected in behavioral changes to either DA receptor agonists or antagonists. Therefore, all dopaminergic behavioral changes do not result from alterations in DA receptors and changes in DA receptors do not necessarily dictate altered behavioral responses to dopaminergic agents.
Animals↗
Hypophysectomy does not alter the increase in striatal dopamine receptor density produced by 6-hydroxydopamine lesions in male rats.
While hypophysectomy can alter the increase in striatal dopamine (DA) receptor density observed after estrogen, haloperidol or prolactin treatments, it does not alter the increase in density found after 6-hydroxydopamine lesions of the DA neurons in male rats. This observation suggests that striatal DA receptors can be regulated by at least two distinct mechanisms, only one of which requires the availability of pituitary hormones.
Animals↗
Modulatory role for prolactin in the elevation of striatal dopamine receptor density induced by chronic treatment with dopamine receptor antagonists.
The chronic administration of haloperidol (HAL), domperidone (DOM), or sulpiride (SUL) increased the density of striatal dopamine (DA) receptors in intact but not in hypophysectomized (Hypox) male rats. This effect was independent of changes in body weight of the rats and of the drugs' abilities to produce cataleptic behavior. All treatments of intact rats increased serum rat prolactin (rPRL) concentrations, while Hypox rats had rPRL levels equivalent to zero. At the doses used in these studies, the striatal DA receptor densities were increased only if the rPRL levels were also increased. Chronic cysteamine (CYS) treatment decreased body weight gain, acutely decreased cataleptic behavior to HAL, decreased serum rPRL levels, and prevented the increase in serum rPRL levels due to HAL administration. While CYS itself did not alter striatal DA receptor density, it prevented the increase in density associated with the chronic administration of HAL (1 mg/kg). Since CYS decreased rPRL levels, these results lend further support to the hypothesis that rPRL (and prolactin in general) is a pituitary hormone with modulatory action on the increase in striatal DA receptor density.
Animals↗
Elevation of striatal dopamine receptors by estrogen: dose and time studies.
Administration to male rats of a single dose of 17 beta-estradiol valerate (8-500 micrograms/rat) or implantation of a pellet containing 17 beta-estradiol (0.5-50 mg/rat) increased serum 17 beta-estradiol levels in a dose-dependent relationship when measured on the sixth day after administration. At the same time, after these doses, the serum rat prolactin (rPRL) levels were doubled and the striatal 3,4-dihydroxyphenylethylamine (DA, dopamine) receptor densities were increased 20%. A single dose of 17 beta-estradiol valerate of 4 micrograms/rat or less did not alter serum 17 beta-estradiol or rPRL levels or the striatal DA receptor density. After the single injection of 17 beta-estradiol valerate (125 micrograms/rat) the serum 17 beta-estradiol levels peaked at 1 day, the serum rPRL levels peaked at 2 days, and the striatal DA receptor density elevation peaked from 4 to 8 days. Implantation of a pellet containing 17 beta-estradiol (25 mg/rat) produced a constant elevation of serum 17 beta-estradiol levels from 1 to 10 days. Whereas the serum rPRL levels were continuously elevated about two-fold, the densities of the striatal DA receptors were increased significantly by 20-25% only from 4 to 8 days after pellet implantation. These results indicate that striatal DA receptor density rises and returns to control levels during the constant elevation of serum 17 beta-estradiol and rPRL levels.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
[3H]Spiperone binding in the rat striatum during the development of physical dependence on phencyclidine and after withdrawal.
Binding of [3H]spiperone to dopamine D2 receptors was measured in the striatum of male rats that were infused with phencyclidine (PCP, 45 mg/kg per day) or vehicle (saline) via an intrajugular cannula for 1, 3.5, or 7 days. The 7-day PCP infusion, which was shown previously to induce physical dependence, produced a significant 30% decrease in receptor density (Bmax). Two days after termination of the 7-day PCP infusion, Bmax values were no longer significantly lower than those of saline-infused controls. The acute administration of PCP (20 mg/kg, i.p.) did not alter receptor density 45 min later.
Animals↗
Possible dissociation of central dopamine receptor antagonism and cataleptic behavior.
A new chemical, 2-[4-[4-(7,9-dioxo-6-thia-8-azaspiro[4,4] nonan-8-yl)-butyl]-1-piperazinyl]pyridine-3-carbonitrile hydrochloride (MJ-13980-1), referred to in this report as MJ-13980, displaced in vitro [3H]spiperone binding, elevated serum prolactin concentrations, and decreased apomorphine-induced stereotyped behavior in male rats. These indicated that MJ-13980 acts as a dopamine (DA) receptor antagonist. However, MJ-13980 (10 mg/kg) elicited only a very small amount of cataleptic behavior and antagonized that produced by haloperidol (HAL), a classical DA receptor blocker and potent inducer of cataleptic behavior. At a lower dose, MJ-13980 (1.0 mg/kg) produced no cataleptic behavior but against decreased that produced by HAL. These results suggest that the antagonistic interaction of MJ-13980 at central DA receptors is not associated with the production of cataleptic behavior.
Animals↗
Effects of lithium on [3H](-)quinuclidinyl benzilate [( 3H](-)QNB) binding to rat brain muscarinic cholinergic receptors.
Addition of lithium in vitro inhibited the binding of [3H](-)QNB to muscarinic cholinergic receptors of homogenates of tissue prepared from the striatum, cortex, and hippocampus of rat brain. Chronic in vivo exposure of rats to lithium in their food produced serum levels of lithium comparable to therapeutic levels. After in vivo exposure, the tissue homogenates prepared from these rats had an apparent decrease in receptor density in the three brain areas. However, if the tissue homogenates were washed twice, before addition to the assays, no differences in binding were detectable. Similar effects on unwashed and washed tissue homogenates can be demonstrated after in vivo exposure to lithium. Therefore, the apparent decrease in binding after in vivo lithium treatment is probably due to lithium retained in the tissue. No permanent alterations in the muscarinic receptor characteristics were measurable after the removal of the lithium. Nevertheless, in vivo interactions at muscarinic receptors may be important under conditions when therapeutic levels of lithium are present.
Animals↗
Estimation of the apparent affinity of the striatal dopamine receptors for the radioligand[3H]spiperone [( 3H]spiroperidol).
The characteristics of the receptor population labeled by the ligand [3H]spiperone were determined by several experimental procedures. Varying the assay volumes, and hence both the receptor and ligand concentrations, did not alter the specificity for the dopamine (DA) receptor. The density of binding sites estimated from saturation analyses varied little (6%) over a greater than 50-fold tissue concentration range. In contrast, variation in tissue concentration did alter the apparent affinity of [3H]spiperone for the DA receptors more than 16-fold, as determined from saturation analyses. This was most marked at large receptor or tissue concentrations. The standard correction for depletion of the free ligand by that bound to the receptors reduced the range to threefold or 200%. Two separate measurements of the DA receptor affinity, using the rates of association and dissociation and the shift in Ki for DA, gave affinity measurements in the same range as that obtained using low concentrations of receptors in saturation analyses. Therefore, three separate estimates for the affinity of [3H]spiperone binding to the striatal DA receptors agreed that it is probably in the range of 10-15 pM, and single saturation experiments reach this level when the tissue concentration is very low, ie, less than 15 micrograms protein per 1 ml assay volume.
Animals↗
Interaction between methylxanthines and the benzodiazepine receptor.
3H-Flunitrazepam (500 pM) was used to estimate the inhibitory effects of caffeine, theophylline, theobromine and 3-methylxanthine on binding to rat brain homogenates. Caffeine and theophylline showed a low affinity competitive type of inhibition in vitro, but no inhibition in vivo. Low concentrations of caffeine failed to show clear inhibitory capabilities against low concentrations of 3H-flunitrazepam. The results suggest that only the toxic central nervous system effects of methylxanthines are mediated via the benzodiazepine receptor.
Animals↗
Hypophysectomy reduces the haloperidol-induced changes in striatal dopamine receptor density.
The ability of haloperidol (HAL) at doses of 1, 2 and 4 mg/kg to increase the density of the striatal dopamine (DA) receptors was measured in normal and hypophysectomized (Hypox) male rats. In intact rats HAL significantly increased the receptor density at all three doses. In Hypox rats HAL produced significantly less of an increase, with only the 4 mg/kg dose producing a statistically significant increase. Therefore, Hypox appears to reduce the ability of HAL to increase striatal DA receptor density.
Analysis of Variance↗
Prolactin increases the density of striatal dopamine receptors in normal and hypophysectomized male rats.
Administration of prolactin to adult male rats, by S.C. injection, significantly increases the density of the striatal dopamine (DA) receptors, without altering the apparent affinity of the receptors for [3H]spiroperidol. Larger doses of prolactin are required to increase the density of the striatal DA receptors in hypophysectomized rats compared to normal rats. These results suggest that prolactin might be the common mediator of the increase in striatal DA receptor density produced by either estrogen or haloperidol administration. Monitoring and/or altering prolactin levels might be informative in neurologic or psychiatric disorders involving striatal DA neurotransmission.
Animals↗
Neurotoxic aspects of porphyrinopathies: lead and succinylacetone.
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5-Aminolevulinate Synthetase↗