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H L Komiskey

Publications and source records attributed to H L Komiskey.

At least 19 recordsLinked to original sources
PubMed1997

Modulation of a competitive N-methyl-D-aspartate receptor antagonist binding by zinc oxide.

Zinc through a zinc binding site is known to modulate the binding of agonists at the NMDA receptor. In the present study, the ability of zinc oxide to alter the specific binding of [3H]CGP-39653, a competitive NMDA receptor antagonist, was determined in homogenate of rat brain tissue. Analysis of saturation experiments indicated that zinc oxide significantly increased the Kd without changing Bmax of [3H]CGP-39653 binding. Furthermore, the effect of ZnO on glutamate and glycine displacement of [3H]CGP-39653 binding was determined. The results of the [3H]CGP-39653 displacement study indicated that ZnO decreases the glutamate and glycine displacement of [3H]CGP-39653 binding.

2-Amino-5-phosphonovalerate↗
PubMed1988

Aging: modulation of GABAA binding sites by ethanol and diazepam.

Modulation of gamma-aminobutyric acid (GABA) binding to the GABAA recognition site by ethanol and/or diazepam appears to change with the age of the animal. Brain tissue above the cerebellum of young, mature, and old rats was examined for an age-related change in the GABAA recognition sites 5 min after the rat was last habituated or received a single injection of the vehicle, ethanol and/or diazepam. The dose of ethanol injected was reduced in the senescent rats, so the brain levels of ethanol did not vary with age. An injection of ethanol and/or diazepam (180 micrograms/kg) did not significantly alter the GABAA recognition site in any age group relative to the habituated or vehicle-injected rats of that age group. However, the affinity of the GABAA recognition site was decreased by ethanol in mature and old rats relative to the affinity of the GABAA site after diazepam pretreatment in the presence and absence of ethanol, respectively. Finally, the combination of ethanol and diazepam elicited an increase in the number of GABAA binding sites relative to diazepam pretreatment in only the young rats. The present results indicate that the GABAA binding site is modulated by ethanol and diazepam in an age-dependent manner.

Aging↗
PubMed1988

Aging: changes in a passive-avoidance response with brain levels of temazepam.

Acute intravenous (IV) injections of temazepam were examined for the ability to impair the performance of young (3-4-month-old), mature (12-15-month-old) and old (28-30-month-old) male Fischer 344 rats in the step-down task relative to vehicle-injected controls. The effect of temazepam on the passive-avoidance response could be characterized as a U-shaped function of age. The performance of the mature rat was not significantly impaired by an IV injection of temazepam between 18 and 320 micrograms/kg. Temazepam was more effective in impairing the performance of the young and old rat. The brain levels of temazepam after a single IV injection of 18 micrograms/kg in mature and senescent rats, and 32 micrograms/kg in young rats were measured over a 2-hour time period. The brain of the mature rat was exposed to less temazepam between 0 and 120 minutes than the brain of the old rat. Therefore, the increased sensitivity of the senescent rat relative to the mature rat may in part be due to changes in the pharmacokinetics of temazepam. However, the inability of temazepam (between 18 and 320 micrograms/kg) to impair the performance of mature rats in the passive-avoidance task suggests that pharmacodynamic changes may be involved in the decreased sensitivity of mature rats relative to young and senescent rats.

Aging↗
PubMed1987

Effect of aging on anticonflict and CNS depressant activity of diazepam in rats.

Male Fischer 344 rats were examined for an age-dependent sensitivity to the anticonflict and central nervous system (CNS) depressant effects of diazepam. A conflict paradigm was used to measure the ability of single intravenous injections of diazepam to attenuate punishment-induced suppression of behavior and to elicit CNS depression in young, mature, and senescent rats. Senescent rats had the lowest behaviorally active threshold dose. However, diazepam at the behaviorally active threshold dose produced a simultaneous increase in punished and unpunished responding in all three age groups. Punished responding was increased more and over a wider dose range in the young and mature rats than in the senescent rats. Sensitivity to the CNS depressant effects of diazepam was over four times greater in the senescent rats than in the other two age groups. In summary, the results indicate that the behavioral effects of diazepam vary with dosage and age of the rat. The male Fischer 344 rat may be a useful animal model for exploring how diazepam elicits age-related behavioral effects in humans.

Aging↗
PubMed1987

Aging: effect on ex-vivo benzodiazepine binding after a diazepam injection.

Ex vivo [3H]flunitrazepam receptor occupation was determined in the brain of young, mature and old male Fischer 344 rats after a single intravenous injection of a low dose of diazepam. The two benzodiazepine receptor subtypes or conformations (BZ1 and BZ2) were differentiated by the displacement of [3H]flunitrazepam specific binding with the triazolopyridazine, CL 218,872. The acute diazepam injection decreased ex vivo [3H]flunitrazepam binding in only the senescent rats. The [3H]flunitrazepam binding at both the BZ1 and BZ2 receptor or receptor conformation was significantly reduced in the old rats.

Aging↗
PubMed1985

Aging: effect on the interaction of ethanol and pentobarbital with the benzodiazepine-GABA receptor-ionophore complex.

Benzodiazepine receptor binding and modulation by pentobarbital and ethanol was studied using the detergent 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate to solubilize the gamma-aminobutyric acid (GABA)-benzodiazepine receptor-ionophore complex from the brains of Fischer 344 rats of 3-4, 12-15 and more than 28 months of age. The affinity of the benzodiazepine binding site was significantly lower in the young rats compared to either the mature or senescent animals. However, no age-related changes in the maximum number of benzodiazepine binding sites or GABA concentrations occurred in the detergent extract. Pentobarbital produced practically identical dose-dependent enhancement of [3H]flunitrazepam specific binding in all 3 age groups. In contrast, ethanol between 0.1 and 200 microM failed to produce a dose-dependent effect on [3H]flunitrazepam specific binding in any age group. The effect of pentobarbital and ethanol on [35S]t-butyl-bicyclophosphorothionate [( 35S]TBPS) specific binding to the picrotoxinin binding site was examined in the above solubilized receptor/ionophore complex under the same binding conditions. Both sedative-hypnotics produced a dose-dependent decrease in [35S]TBPS specific binding. However, pentobarbital was over 10,000 times more potent. It appears that ethanol may not enhance [3H]flunitrazepam specific binding in this solubilized preparation because of its weak action at the picrotoxinin binding site.

Aging↗
PubMed1984

Aging: effects on beta-carboline binding in hippocampal subfields.

The CA1 and CA4/area dentata subfields of the hippocampus in young, mature and old rats were examined for age-related change in propyl beta-carboline-3-carboxylate (PrCC) binding. 3H-PrCC bound with high affinity (Kd = 0.82 nM) to one binding site when ethyl beta-carboline-3-carboxylate was used to delineate specific binding. An age dependent change in the maximum number of 3H-PrCC binding sites in the CA1 and CA4/area dentate subfields of the hippocampus were assessed by using a saturating (6 nM) concentration of 3H-PrCC. Although 3H-PrCC specific binding at a saturating concentration (6 nM) was significantly less in both the CA1 and CA4/area dentata subfields of the senescent rat, the magnitude of the decrease was greater in the CA1 region. In addition, the affinity of the 3H-PrCC binding site in both subfields probably did not vary significantly with age. Therefore, the CA1 and CA4/area dentate of the rat hippocampus may not only lose BZ1 receptors or the BZ1 receptor conformation with age, but the severity of receptor or receptor conformation loss varies with the subfield.

Aging↗
PubMed1983

Effect on neuronal and non-neuronal benzodiazepine binding sites.

The frontal cortex, hippocampus, and cerebellum of the Fischer 344 rat were examined for an age-dependent change in neuronal and non-neuronal binding. Clonazepam and Ro5-6669 displaceable [3H]diazepam binding were used as indicators of [3H]diazepam binding on neuronal and non-neuronal membranes, respectively. In both the frontal cortex and the hippocampus, clonazepam displaceable [3H]diazepam binding in the senescent rat was significantly less than the young and mature rat. In the frontal cortex, Ro5-6669 did not significantly displace [3H]diazepam binding in any age group. The Ro5-6669 displaceable [3H]diazepam binding in the hippocampus was not altered with age. In the cerebellum clonazepam and Ro5-6669 displaceable binding in the old rat was significantly less and more, respectively, compared to the young rat.

Aging↗
PubMed1982

Phencyclidine-induced release of [3H]dopamine from chopped striatal tissue.

Phencyclidine was examined for its ability to release [3H]dopamine ([3H]DA) from prelabelled chopped rat striatal tissue. A dynamic perfusion system was used in order to minimize the effects of drugs on uptake mechanisms. Cocaine and S-(+)-amphetamine were used to distinguish uptake inhibition from a neurotransmitter releasing action. Phencyclidine, starting at 3 microM caused a dose-dependent increase in efflux of [3H]DA from chopped striatal tissue. In this same preparation, cocaine, a known neuronal uptake inhibitor of dopamine, was unable to release [3H]DA except in the largest dose of 100 microM. S-(+)Amphetamine, a known releaser of neuronal dopamine, was found to be about ten times more potent then phencyclidine in causing a dose-dependent release of [3H]DA. The results of the above experiments are discussed in relation to the ability of phencyclidine to decrease the synaptosomal accumulation of [3H]DA. It is concluded that some of the psychoactive effects of phencyclidine may be due to the ability of phencyclidine to elicit a release of dopamine from dopaminergic neurons.

Animals↗
PubMed1980

Basis of phencyclidine's ability to decrease the synaptosomal accumulation of 3H-catecholamines.

Mixed cortical and hypothalamic synaptosomes and striatal synaptosomes were allowed to accumulate 3H-norepinephrine and 3H-dopamine, respectively, for 5 min in the absence and presence of phencyclidine. The results indicate that phencyclidine probably decreased the accumulation of 3H-norepinephrine into mixed cortical and hypothalamic synaptosomes by only blocking the uptake of the 3H-amine. On the other hand, part of the decrease in accumulation of 3H-dopamine elicited by 10 muM of PCP was probably caused by PCP releasing previously accumulated 3H-dopamine.

Animals↗
PubMed1978

Inhibition of synaptosomal uptake of norepinephrine and dopamine by conformationally restricted sympathomimetic amines.

The conformationally restricted cis and trans isomer of substituted cyclobutanes were examined for their ability to inhibit 3H-norepinephrine and 3H-dopamine accumulation by synaptosomes prepared from the cortex and corpus striatum, respectively. The drugs were more effective in preventing the accumulation of 3H-norepinephrine by cortical synaptosomes than 3H-dopamine by striatal synaptosomes. However, in the synaptosomes isolated from both regions, the trans isomers were more potent inhibitors of accumulation than the cis isomers. The greatest stereoselectivity was exhibited by the isomers of 2-amino-1-phenylcyclobutanol. The accumulation of 3H-norepinephrine by cortical synaptosomes and the accumulation of 3H-dopamine by striatal synaptosomes were inhibited 50% by concentrations of the trans isomer of 7.4 X 10(-6) M and 1.7 X 10(-4) M, respectively. The cis isomer was inactive. In separate experiments, the releasing capabilities of the restricted analogs were determined by superfusing cortical and striatal synaptosomes labelled in vitro with 3H-catecholamines. The trans and cis isomers elicited a trivial release of 3H-norepinephrine and 3H-dopamine from cortical and striatal synaptosomes, respectively. The results indicate that the decreased synaptosomal accumulation of 3H-catecholamines caused by the analogs was due mainly to inhibition of uptake. The influence of dihydral angle between phenyl--NH2 on the inhibition of uptake is discussed. It is concluded that the anti conformation of sympathomimetic amines is the preferred conformation at the noradrenergic amine pump.

Aminophenols↗
PubMed1978

Conformation of dopamine at the dopamine receptor.

Tritiated dopamine was used to label the dopamine receptor in membranes isolated from the rat corpus striatum. Scatchard analysis of displacement of [3H]dopamine by nonradioactive dopamine indicated the presence of two binding sites. The similarities in affinity, capacity, and drug specificity of the high-affinity site in the striatal membranes from rat and the binding site in the membranes from the calf caudate nucleus suggest that [3H]dopamine labels the same site in both species. In order to determine what conformation of dopamine is preferred at the dopamine receptor site, conformationally restricted analogs of dopamine--namely, the cis and trans 2-amino-1(3,4-dihydroxyphenyl)cyclobutane hydrochlorides--were tested for their affinity to the receptor. Compared to the cis conformation, the trans-restricted analogs had more affinity for the receptor site, indicating that dopamine probably interacts with the receptor in the trans conformation.

Animals↗
PubMed1975

The involvement of methysergide-sensitive receptors and prostaglandins in the hyperthermia evoked by 5-HT in the cat.

In the unanesthetized cat, an injection of 0.01 or 0.03 M 5-hydroxytryptamine into the rostral hypothalamus produced an immediate, short-lasting increase or decrease in body temperature. A delayed and long-lasting hyperthermia often followed the initial response. When indomethacin, 10 mg/kg, was administered intraperitoneally 3 hours prior to an injection of 5-hydroxytryptamine at sites which produced an initial increase in body temperature, the secondary hyperthermia was reduced or abolished but the immediate response remained undiminished. Pretreatment with methysergide, 2 mg/kg i.p., attenuated or abolished the initial temperature increase but did not reduce the delayed hyperthermia. The results suggest that the initial rise in body temperature produced by 5-hydroxytryptamine is mediated by activation of methysergide-sensitive 5-HT receptors and that the response is independent of prostaglandin release. The secondary hyperthermia, on the other hand, is apparently mediated by a sustained release of prostaglandins.

Analysis of Variance↗