Biomedical subjects

J S Hong

Publications and source records attributed to J S Hong.

At least 163 records · Page 9Linked to original sources

PubMed1989

Glucocorticoids potentiate kainic acid-induced seizures and wet dog shakes.

Glucocorticoid effects on kainic acid-induced motor seizures and wet dog shakes in rats were investigated by adrenalectomy and dexamethasone treatment. One-day adrenalectomy attenuated kainic acid-induced wet dog shakes and seizure activity. These effects were restored by dexamethasone. Administration of dexamethasone to non-adrenalectomized rats potentiated kainic acid-induced wet dog shakes and severity of seizure activity. These results suggest that glucocorticoids may play an important role in modulating the severity of kainic acid-induced seizures and wet dog shakes.

Adrenalectomy↗

PubMed1989

Inter- and intrasubject variations of ranitidine pharmacokinetics after oral administration to normal male subjects.

Inter- and intrasubject variations of ranitidine pharmacokinetics were examined following oral administration of ranitidine tablets (150 mg as base) under controlled conditions at a timed interval of one week (periods I and II) to 12 healthy male subjects. Significant secondary peaks in the plasma concentration-time curves were observed in all subjects in both periods. The first peak occurred at 0.5 to 2.5 h and the second peak at 3 to 6 h after the dosing. There were great variations in the plasma concentration-time profiles among subjects; for example, the area under the plasma concentration-time curve from time 0 to 12 h (AUC0-12) varied from 1905 to 5672 micrograms.h/mL. But bioavailability parameters of period I, such as maximum concentration of the first and second plasma peak (Cmax 1 and Cmax 2, respectively), time to first peak (tmax 1), AUC0-12, and AUC from time zero to infinity (AUC0-infinity), were correlated significantly with those of period II. These results suggest that the intrasubject variation of ranitidine pharmacokinetics is usually small over at least one week under the controlled conditions of this study, in spite of its great intersubject variation.

Administration, Oral↗

PubMed1989

Single or repeated electroconvulsive shocks alter the levels of prodynorphin and proenkephalin mRNAs in rat brain.

The effects of single or repeated electroconvulsive shocks (ECS) on the abundance of mRNAs coding for prodynorphin (DYN mRNA) and proenkephalin (EK mRNA) in rat brain were investigated. Rats were given either a single ECS and sacrificed at 0.5, 2, 6, or 12 h post-shock (expt. I), or were subjected to ECS for 1, 3 or 6 days and killed 24 h after the last shock (expt. II). The amounts of DYN mRNA and EK mRNA were measured in several brain regions using RNA blot analysis. In expt. I, a biphasic change in the DYN mRNA level was found in the hippocampus, with an initial 49% decrease at 0.5 h followed by a 51% increase at 6 h after a single ECS. The EK mRNA content in the entorhinal cortex started to increase at 0.5 h, and continued to rise, reaching 260% of the control level at 12 h post-shock. A smaller increase in the EK mRNA level was found also in the hippocampus at 2 to 12 h post-shock. No significant increase in [Met5]-enkephalin or dynorphin A(1-8) immunoreactivity was detected by radioimmunoassay in either area. In expt. II, a dramatic reduction in the DYN mRNA level was observed in the hippocampus 24 h after a single or repeated ECS. In contrast, elevated DYN mRNA levels were seen in the striatum and hypothalamus. The EK mRNA level remained elevated in the entorhinal cortex after 6 daily ECS.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1989

Changes of proenkephalin and prodynorphin mRNAs and related peptides in rat brain during the development of deep prepyriform cortex kindling.

The effects of deep prepyriform cortex (DPC) kindling on the amount of proenkephalin and prodynorphin mRNAs, Met5-enkephalin (ME) and dynorphin (DYN) in rat brain were examined. Animals received electrical stimulation of the DPC until two consecutive stage 2 seizures (S2) or stage 5 seizures (S5) were attained. The proenkephalin mRNA and ME contents in the entorhinal cortex were increased 24 h after S2 and also 5 min and 24 h post S5. In the hippocampus, the proenkephalin mRNA level was reduced 24 h after S2 but increased 5 min and 24 h after S5. Elevated hippocampal ME concentration was observed 24 h after S2 and S5. Similarly, the ME level in the frontal cortex was increased 24 h after S2 and S5 but the proenkephalin mRNA content was only elevated at S5. In the striatum, the proenkephalin mRNA level was slightly increased 24 h after S2 and S5, but no change in ME content was found. The amount of prodynorphin mRNA in the hippocampus was attenuated only at 24 h after S5, whereas DYN concentration was reduced 5 min after S5. No change in striatal DYN concentration was observed despite a slight elevation of prodynorphin mRNA 24 h post S2 and S5. Six weeks after the last seizure, no difference in ME and DYN was found between kindled and control animals. These findings indicate that the enkephalin-containing perforant pathway in the entorhinal cortex-hippocampal region is particularly sensitive to electrical stimulations applied to the DPC. Its role and importance in the development of kindling are discussed.

Animals↗

PubMed1989

Elevated dynorphin in the hippocampal formation of aged rats: relation to cognitive impairment on a spatial learning task.

Radioimmunoassay revealed increased dynorphin A(1-8)-like immunoreactivity [dynA(1-8)LI] in the aged rat brain. Among a number of brain regions examined, an age-related dynA(1-8)LI elevation was found only in the hippocampal formation and frontal cortex. Moreover, the increase in dynA(1-8)LI in the aged hippocampus was associated with a decline in spatial learning ability: dynA(1-8)LI distinguished aged rats that were behaviorally impaired from aged cohorts that learned the spatial task as rapidly as younger animals. Northern blot hybridization using a 32P-labeled complementary RNA probe encoding rat prodynorphin indicated that the abundance of prodynorphin mRNA was also significantly increased in the hippocampal formation of aged rats with identified spatial learning impairments.

Aging↗

PubMed1989

Lithium increases rat striatal beta- and gamma-preprotachykinin messenger RNAs.

Previous reports indicate that the antimanic drug, lithium, increases substance P-like immunoreactivity (SP-LI) in the basal ganglia. The aim of this study was to use lithium as a pharmacological tool to further understand the mechanism of this process. We have used solution hybridization-nuclease protection assays to quantitate the specific preprotachykinin (PPT) mRNAs and radioimmunoassays and immunocytochemistry to assess SP-LI levels in the striatum of male Fisher F-344 rats. A regimen of subchronic administration of lithium (4 mEq/kg i.p. for 1, 2, 4 or 6 days) increased SP-LI in a time-dependent fashion. Concurrent administration of a dopamine receptor antagonist, haloperidol (1 mg/kg s.c. for 4 days) with a 4-day lithium regimen partially blocked the lithium-induced increase in SP-LI as well as neurokinin A-like immunoreactivity. An analysis of the abundance of individual PPT mRNAs indicated that lithium increases beta- and gamma-PPT mRNAs in the striatum; coadministration of haloperidol attenuates the lithium-induced increases. These results indicate that lithium affects the tachykinin biosynthetic process by accelerating transcriptional and/or translational processes in striatonigral neurons and that the dopaminergic system appears to be partly involved in this process.

Animals↗

PubMed1989

Opioids induce convulsions and wet dog shakes in rats: mediation by hippocampal mu, but not delta or kappa opioid receptors.

The opioid receptor subtypes and brain regions involved in eliciting convulsions and wet dog shakes (WDS) were studied by testing different opioid receptor selective agonists in unanesthetized rats. Selective mu agonists, [NMe-Phe3-D-Pro4]-morphiceptin (PL017) and [D-Ala2-N-methyl-Phe3-Gly5-ol]-enkephalin, induced convulsions and WDS when unilaterally injected into the ventral hippocampus. [D-Ala2,D-Leu5]-enkephalin (DADLE), a mixed mu and delta agonist, also elicited such behavioral changes, but its effect was less potent than the selective mu agonists. DADLE-induced WDS were dose dependent, and both convulsions and WDS were antagonized by the irreversible mu receptor antagonist, beta-funaltrexamine, but not by the selective delta receptor antagonist, ICI-174,864. Treatment with the selective delta agonist [D-Pen2,5]-enkephalin or the selective kappa agonists U-50,488H, dynorphin-A amide, or dynorphin-A(1-8) did not produce convulsions or WDS. The injection of a high dose of PL017 intraventricularly or into other brain regions such as the dorsal hippocampus, frontal cortex, striatum, and amygdala did not produce convulsions or WDS, therefore suggesting the ventral hippocampus is an important site for the expression of opioid-induced convulsions and WDS. These results suggest that opioid-induced convulsions and WDS are mediated exclusively by mu but not delta or kappa opioid receptors in the ventral hippocampus.

Animals↗

PubMed1989

Behavioral and neurochemical effects of orally administered MDMA in the rodent and nonhuman primate.

MDMA (methylenedioxymethamphetamine) is a recreational drug of abuse known as "Ecstasy" which markedly decreases regional brain serotonin (5-HT) content and produces 5-HT nerve terminal degeneration in forebrain areas of the rat. In order to determine the acute and chronic behavioral effects of MDMA, adult rats were given MDMA at 0, 5 or 10 mg/kg, po for 4 consecutive days. Alternatively, parachloroamphetamine (PCA) at 5 mg/kg was administered under the same regimen. Within 30 min after the first dose, the MDMA-treated rats exhibited the serotonin motor syndrome consisting of straub tail and splayed hindlimbs comparable to that seen in the PCA-treated rats. This serotonin motor syndrome, with a duration of about 2 hr, was less pronounced after subsequent doses. At 2-4 wk after the last dose, no significant differences between control and treated rats were seen in emergence, hot plate response, auditory startle response or complex maze behavior even though a significant dose-related decrease (50%) in 5-HT concentration was observed in the frontal cortex and hippocampus of these rats 4 wks after the last dose. Adult female monkeys dosed po with 5 or 10 mg/kg of MDMA twice/day for 4 consecutive days demonstrated no spontaneous behavioral changes or weight loss compared to controls, but forebrain 5-HT concentration was reduced by 80% 1 mon after dosing. These data indicate that at doses only 2-3 times the human dose, MDMA produces significant forebrain 5-HT decreases but does not produce detectable residual behavioral alterations as assessed by these behavioral paradigms.

3,4-Methylenedioxyamphetamine↗

PubMed1989

Oral administration of aspartame is not proconvulsant in rats.

These experiments examined the potential for single or repeated doses of aspartame to exacerbate or facilitate the production of seizures in Fischer-344 rats. In adult animals, 1,000 mg/kg of aspartame given by gavage acutely or over a 14 day period had no significant effect on the rate of kindling induced by stimulation of the prepyriform cortex. A single dose of 1,000 mg/kg of aspartame had no effect on the number of animals developing tonic seizures after electroconvulsive shock, nor did aspartame affect the frequency or duration of seizure activity after pentylenetetrazol. In a second series of studies, young male and female rats were dosed with 1,000 mg/kg of aspartame on day 3-13 or 21-35 of age. Prior exposure to aspartame had no significant effect on the rate of kindling at 90 days of age. These experiments indicate that aspartame does not act a pro-convulsant in rats.

Administration, Oral↗

PubMed1988

Increased dopamine release from striata of rats after unilateral nigrostriatal bundle damage.

Dopaminergic control of striatal neurons is retained in rats sustaining lesions of the nigrostriatal bundle (NSB) as long as 10% of the projection remains, suggesting that enhanced efficiency of dopamine (DA) transmission may compensate for the denervation of the striatum. To examine this hypothesis we have studied the extracellular concentration of striatal DA using brain dialysis. In control rats, haloperidol (1 mg/kg, i.p.) or depolarization of striatal tissue with 25 mM KCl increased, and gamma-butyrolactone (500 mg/kg, i.p.) decreased DA and homovanillic acid (HVA) levels in striatal dialysates. Three weeks after unilateral injection of 6-hydroxydopamine (6-OHDA) to substantia nigra, DA content in the ipsilateral striatum was decreased by 60-98%. Nevertheless, extracellular DA concentration in the lesioned striata remained unchanged in rats with 60-90% DA depletions. More extensive lesions (96% DA depletion) were accompanied by 60% reduction in DA release. In contrast, extracellular HVA levels in the lesioned striata decreased proportionally to the depletion of tissue DA, indicating decreased inactivation of extracellular DA. We propose that the capacity of the residual DA terminals to maintain normal levels of extracellular DA after 60-90% NSB lesions may serve to compensate for the partial denervation of the striatal tissue. Disruption of striatal DA functions and postsynaptic supersensitivity after more extensive lesions may be associated with the failure of the NSB to fully compensate for loss of DA terminals. In striata contralateral to the 6-OHDA lesions, increased DA release was also observed. In addition, 60-90% ipsilateral DA depletions were accompanied by 32% and 42% increases in DA and HVA content in contralateral tissue, respectively. The possibility of the contralateral sprouting of DA terminals is discussed.

4-Butyrolactone↗

PubMed1988

Intrahippocampal injections of a specific mu-receptor ligand PL017 produce generalized convulsions in rats.

The effects of a selective mu-agonist, [NMe-Phe3-D-Pro4]morphiceptin (PL017), and a selective mu-antagonist, beta-funaltrexamine (beta-FNA), on convulsions and wet dog shakes (WDS) were studied. Electroencephalogram demonstrated that a single injection of PL017 into the ventral hippocampus evoked epileptiform spiking which appeared initially in the ventral hippocampus and spread to the cortical area when the animal developed generalized convulsion. Behavioral studies showed that PL017-induced convulsions and WDS were dose-dependent, and these behavioral changes were blocked by beta-FNA pretreatment. The results indicate that mu-receptors in the hippocampus may play an important role in seizure activities evoked by opioids.

Animals↗

PubMed1988

Ganglioside interactions with the dopaminergic system of rats.

The effects of ganglioside treatment on changes in dopaminergic function following 6-hydroxydopamine (6-OHDA) or repeated exposure to haloperidol were studied in male Fischer-344 rats. Rats were injected sc with 30 mg/kg of a mixed ganglioside preparation (GM) at the time of the surgery and for 13 days after receiving an intranigral injection of 6-OHDA. GM treatment attenuated 6-OHDA depletion of striatal dopamine (DA) and DOPAC. Another group of rats was implanted with chronic indwelling cannulas in the lateral cerebroventricles at the time of 6-OHDA administration into the substantia nigra. Daily intraventricular injection of 25 or 50 micrograms GM attenuated depletions of striatal DA and DOPAC. A separate experiment sought to determine the effects of GM1 on the development of receptor supersensitivity produced by repeated exposure to a dopamine receptor antagonist. Rats were injected sc with 1 mg/kg haloperidol for 8 or for 16 days; some rats were coadministered 20 mg/kg GM1 sc. Four days after the last dose, the rats were challenged with 1 mg/kg apomorphine, and activity was counted for 60 min. Treatment with GM1 decreased the behavioral supersensitivity to apomorphine induced by repeated exposure to haloperidol. These experiments suggest that treatment with GM can have a protective effect against 6-OHDA-induced depletion of dopamine if treatment with GM begins at the time of lesioning. These studies also support receptor binding data from other laboratories indicating that treatment with GM1 can affect up-regulation of dopamine receptors.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1988

Roles of the pituitary-adrenocortical axis in control of the native and cryptic enkephalin levels and proenkephalin mRNA in the sympathoadrenal system of the rat.

The effects of hypophysectomy (HPX) and dexamethasone (DEX) on the levels of Met5-enkephalin (ME), ME precursors, and the abundance of proenkephalin (pEK) mRNA, were examined in the adrenal medulla (AM) and superior cervical ganglia (SCG). To assess possible changes in enkephalin processing, both cryptic (after trypsin and carboxypeptidase B digestions) and native (without enzyme digestions) ME-like immunoreactivity (ME-LI) was measured. Three weeks after HPX the proportion of pEK mRNA to the total RNA content in the AM was not significantly changed when compared to sham-operated (SO) animals. Total (native + cryptic) ME-LI was decreased by 45% in the AM of HPX rats. This decrease was paralleled by a 58% depletion of AM proteins. Cryptic ME-LI was also reduced by 43%. In contrast, native ME-LI was not altered after HPX, indicating enhanced processing of ME precursors. Treatment with DEX (5 daily injections--1 mg/kg, i.p.) increased the relative abundance of pEK mRNA (+27%) and total ME-LI in the AM of HPX group, but not in SO group. Native ME-LI, cryptic ME-LI, and their ratio were not significantly affected by DEX in the AM of HPX or SO rats. In SCG, the relative abundance of pEK mRNA decreased by 25% after hypophysectomy. Total and cryptic ME-LI in the SCG of HPX rats were not changed when compared to SO rats. In contrast, HPX reduced native ME-LI suggesting decreased processing of ME precursors. Similarly, as in AM, DEX produced increase in the SCG pEK mRNA only in HPX (+68%) and not in the SO rats. In SCG, DEX produced decreases in total ME-LI which could be attributed to an increased enkephalin release. An overall reduction of cryptic ME-LI was also observed after DEX, whereas native ME-LI remained unchanged suggesting increased processing of enkephalins. Our findings indicate that the pituitary adrenocortical axis controls the relative proportions of ME to its precursors, and that this control involves both glucocorticoid-dependent (SCG) and glucocorticoid-independent (AM) mechanisms. In contrast, our studies do not suggest specific control of pEK synthesis by the pituitary adrenocortical axis. The pituitary adrenocortical axis may also influence the relative contents of ME and catecholamines in the AM and SCG. The ratio of ME/catecholamines increased after HPX (AM and SCG) and after DEX (SCG). Such regulation may contribute to the control of co-transmitter output in the sympathoadrenal system.

Adrenal Medulla↗

PubMed1988

Regulation of tyrosine hydroxylase and phenylethanolamine N-methyltransferase mRNA levels in the sympathoadrenal system by the pituitary-adrenocortical axis.

The pituitary-adrenocortical axis plays a complex role in the regulation of the levels of enzymes of the catecholamine biosynthetic pathway. In this report we have explored molecular mechanisms of these regulations, by examining the effects of hypophysectomy (HPX) and dexamethasone (DEX) on tyrosine hydroxylase (TH) and phenylethanolamine N-methyltransferase (PNMT) mRNA levels in the adrenal medulla (AM) and superior cervical ganglia (SCG). Three weeks after hypophysectomy weights (-48%), total RNA (-49%), and DNA (-22%) contents in AM were significantly reduced, when compared to sham-operated animals (SO). In SCG decreases in weight (-23%) and in the ratio of RNA/DNA (-25%) were also found. TH mRNA contents paralleled decreases in total RNA levels and no significant change in the relative abundance of TH mRNA was found. When HPX rats were injected for 5 days with DEX (1 mg/kg, i.p.), TH mRNA levels in the SCG (+51%) and in the AM (+74%) were significantly increased when compared to saline-treated HPX animals. DEX given to SO rats increased TH mRNA in SCG (+49%); a 27% increase in TH mRNA in the AM was also observed. The relative abundance of PNMT mRNA in the AM was reduced after hypophysectomy (-64%). This decrease was completely reversed by DEX. In contrast, DEX did not affect PNMT mRNA levels in the AM of SO rats. PNMT mRNA was not detected in SCG of saline- or DEX-treated rats. In conclusion, our findings suggest that the pituitary-adrenocortical axis is involved in the regulation of the steady-state levels of TH and PNMT mRNAs. This regulation involves: (1) induction of TH mRNA contents in AM and SCG by increased plasma glucocorticoid levels; and (2) maintenance of the steady-state levels of PNMT mRNA in AM by glucocorticoid-dependent mechanisms.

Adrenal Medulla↗

PubMed1988

Lithium increases dynorphin A(1-8) and prodynorphin mRNA levels in the basal ganglia of rats.

The aim of this study was to understand the possible influence of the antimanic drug, lithium, and the neuroleptic, haloperidol, alone or in combination, on the regulation of dynorphin biosynthesis in the striatum. The study was done using male Fisher-344 rats subjected to a regimen of subchronic administration of lithium chloride (4 mEq/kg/day for 1,2,4 or 6 days, i.p.) or a regimen of chronic oral administration of a diet containing lithium carbonate (1.5 g/kg of the diet). Subchronic administration of lithium increased striatal dynorphin A(1-8)-like immunoreactivity (DN-LI) in a time-related fashion. Immunocytochemistry revealed an increase in DN-LI in fibers and cells clustered in 'patches' throughout striatum. The increase in DN-LI was reversible on cessation of lithium administration. Concurrent administration of lithium and an opiate antagonist, naltrexone, or a dopamine receptor antagonist, haloperidol, did not influence the changes induced by lithium. Chronic oral administration of lithium for 21 days led to an increase in DN-LI in the striatum. Co-administration of haloperidol with the 21 day regimen of lithium administration failed to affect the increase in DN-LI. The prodynorphin mRNA abundance in the striatum was quantitated by a molecular hybridization procedure using a prodynorphin 32P-cRNA probe generated from the Riboprobe system. Evidence from the Northern blot analysis reveals that lithium increases the prodynorphin mRNA abundance in the striatum. These results indicate that lithium affects the dynamics of prodynorphin biosynthesis in the striatum, presumably increasing transcription and/or translational processes.

Animals↗

PubMed1988

Nucleotide sequence and transcription start point of the phosphoglycerate transporter gene of Salmonella typhimurium.

We identified the phosphoglycerate transporter gene of Salmonella typhimurium and its polypeptide product and determined the nucleotide sequence of the gene. The predicted translation product was a protein of 406 amino acid residues and was extremely hydrophobic, a feature that is consistent with its role in membrane transport. Hydropathy analysis suggested that there are eight transmembrane segments of at least 20 amino acid residues for the protein. The transcription start point was mapped to lie at position -44 relative to the putative translational initiation start point. Comparison of PgtP with UhpT and GlpT, the membrane-bound proteins involved in the transport of hexose-6-phosphate and glycerol-3-phosphate, respectively, revealed a very high degree of amino acid sequence similarity among them, reflecting not only similar structures and functions among these polypeptides but also a common evolutionary origin for them.

Amino Acid Sequence↗

PubMed1988

Identification of the products and nucleotide sequences of two regulatory genes involved in the exogenous induction of phosphoglycerate transport in Salmonella typhimurium.

We describe the determination of the nucleotide sequence of two genes (pgtB and pgtC) contained within the 3.4-kilobase DNA segment sandwiched between the transporter gene, pgtP, and the regulatory gene, pgtA. These two genes are involved in the regulation of expression of phosphoglycerate transport in Salmonella typhimurium. The sequence indicates the presence of two large open reading frames, potentially coding for two polypeptides of 397 and 593 amino acid residues. The two gene products were identified by using the bacteriophage T7 RNA polymerase-T7 promoter coupled system of Tabor and Richardson, and the observed apparent mass of 45 and 69 kilodaltons correlated well with the respective open reading frames. The cellular location of these two polypeptides was directly determined, and the polypeptides were found to be associated with the membrane. Although overall these polypeptides appear to be hydrophilic, there is one hydrophobic transmembrane segment in the smaller polypeptide and four such segments in the larger polypeptide which can account for their association with the membrane. In the accompanying paper, we present genetic evidence that pgtB and pgtC genes are involved in the induction of the pgtP expression by modulating derepressor activity.

Amino Acid Sequence↗

PubMed1988

Genetic evidence for modulation of the activator by two regulatory proteins involved in the exogenous induction of phosphoglycerate transport in Salmonella typhimurium.

Previous work from this laboratory has identified in a fragment of DNA, cloned from Salmonella typhimurium, two genes involved in the exogenous induction of phosphoglycerate transport. These two genes, the transporter gene, pgtP, and the activator gene, pgtA, are closely linked physically; they are only 3.4 kilobases apart. In the accompanying paper, we describe the determination of the nucleotide sequence of this 3.4-kilobase DNA segment and show that this segment contains two genes, pgtB and pgtC, encoding two polypeptides of 593 and 397 amino acid residues, respectively. This paper presents an analysis of the effects of insertions and deletions in pgtBC on the expression of pgtP gene and on the expression of lacZ fused to the pgtP gene. The results indicate that both pgtBC genes are necessary for expression of the pgtP gene. Strikingly, deletion of both genes resulted in a constitutive phenotype, suggesting that PgtB and PgtC polypeptides modulate PgtA activity. The expression of the pgtP gene appears to be regulated by the pgtA gene product, which acts as an activator. A model of induction is proposed in which the central feature is the interaction of the three regulatory proteins in the membrane such that the activity of the activator (PgtA) is subject to modulation by the binding of an inducer.

Chromosome Deletion↗