• YAKHAK HOEJI
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• v.42 no.1
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• pp.95-100
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• 1998

Male Sprague-Dawley rats were exposed to the toluene at 3,000${\pm}$200ppm via inhalation for two hours (single inhalation group), three weeks by two hours per day, six days per wee k (repeated inhalation group). We examined the level of excitatory amino acids of the extracellular neurotransmitter within the corpus striatum of rats by using in vivo microdialysis. Aspartate (Asp) and glutamate (Glu) of excitatory amino acid neurotransmitters were generally decreased in the inhalation groups compared with the control group, and more significantly decreased in the repeated inhalation group than in the single inhalation group except that Asp was increased from 60 min after the beginning of the inhalation to 30 min after the termination.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1996.04a
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• pp.175-175
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• 1996

The spinal dorsal horn is the area where primary afferent fibers terminate and cutaneous sensory information is Processed. A number of putative neurotransmitter substances, including excitatory and inhibitory amino acids and peptides, are present in this region and sites and cellular mechanisms of their actions have been a target of numerous studies. In this study, single neurons were acutely isolated and the properties of whole cell current and responses to excitatory and inhibitory neurotransmitters were studied by the patch clamp method. Young rats (7-14 days) were anesthetized with diethyl-ether, and the lumbar spinal cord was excised and cut transversely at a thickness of 30$\mu\textrm{m}$ by Vibroslicer. The treatment of spinal slices with low concentration of proteases (pronase and thermolysin 0.75 mg/$m\ell$) and mechanical dissociation yielded isolated neurons with near intact morphology. Multipolar, ellipsoidal and bipolar, and pyramidal cells were shown. By applying step voltage pulses to neurons held at -70 mV, two types of inward currents and one outward currents observed. The fast activating and inactivating inward current was the Na$\^$+/ current because of its fast kinetics and blocking by 0.5${\mu}$M TTX, a specific blocker of Na$\^$+/ channel. The second type of inward currents were sustained. Based on their kinetics and current-voltage relations, it was likely that the second type of inward current was the voltage-dependent Ca$\^$2+/ current. In the presence of TTX, the steady-state currents mainly represented outward K$\^$+/ current which looked like the delayed rectifier K$\^$+/ current. In addition, the membrane currents produced by agonist of excitatory amino acid (EAA) receptor and the endogenous transmitter candidate L-glutamate were recorded in isolated whole-cell voltage clamped neurons as well as responses to inhibitory amino acids (${\gamma}$-amino butyric acid, glycine). Drugs were applied by a method that allows complete exchange of the solution within 1 sec; an infinite number of solutions can be applied to a single cell.

• The Korean Journal of Physiology
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• v.30 no.2
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• pp.289-297
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• 1996

Excitatory amino acids (EAA) are thought to play an important role in producing cell death associated with ischemic and traumatic spinal cord injury. The present study was carried out to determine if the response characteristics of spinal sensory neurons in segments adjacent to degeneration sites induced by EAA are altered following these morphological changes. Intraspinal injections of quisqualic acid (QA) produced neuronal degeneration and spinal cavitation of gray matter. The severity of lesions was significantly attenuated by pretreatment with a non-NMDA antagonist NBQX. In extracellular single unit recordings, dorsal horn neurons in QA injected animal showed the increased mechanosensitivity, which included a shift to the left in the stimulus-response relationship, an increased background activity and an increase in the duration of after-discharge responses. Neuronal responses, especially the C-fiber response, to suprathreshold electrical stimulation of sciatic nerve also increased in most cases. These results suggest that altered functional states of neurons may be responsible for sensory abnormalities, e.g. allodynia and hyperalgesia, associated with syringomyolia and spinal cord injury.

• The Korean Journal of Physiology and Pharmacology
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• v.6 no.5
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• pp.241-246
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• 2002

We studied the excitatory action of morphine on the responses of dorsal horn neuron to iontophoretic application of excitatory amino acid and C-fiber stimulation by using the in vivo electrophysiological technique in the rat. In 137 of the 232 wide dynamic range (WDR) neurons tested, iontophoretic application of morphine enhanced the WDR neuron responses to N-methyl-D-aspartate (NMDA), kainate, and graded electrical stimulation of C-fibers. Morphine did not have any excitatory effects on the responses of low threshold cells. Morphine-induced excitatory effect at low ejection current was naloxone-reversible and reversed to an inhibitory action at high ejection current. NMDA receptor, calcium channel and intracellular $Ca^{2+}$ antagonists strongly antagonized the morphine-induced excitatory effect. These results suggest that changes in intracellular ionic concentration, especially $Ca^{2+},$ play an important role in the induction of excitatory effect of morphine in the rat dorsal horn neurons.

• Biomolecules & Therapeutics
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• v.3 no.1
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• pp.91-96
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• 1995

The effects of toluene inhalation on the contents of amino acid neurotransmitters in rat brain were investigated and blood toluene concentrations inducing changes of behavior and amino acid neurotransmitter contents in rat brain were observed. Male wistar rats were exposed to toluene vapor (single dose : 1700, 5000 and 10000 ppm for 2 hrs, repeated dose : 1700 and 5000 ppm for 2 hrs/day$\times$6 days). Toluene concentrations in blood and the inhalation chamber were assayed by GC with headspace sampler. HPLC method following PITC derivatization was used to measure the amino acid contents in brain tissues such as frontal cortex, caudate, hippocampus, cerebellum and brain stem. Glutamic acid and aspartic acid levels were increased by single inhalation of toluene (5000 ppm) in all the brain areas assayed in this experiment. In caudate and cerebellum, taurine levels were decreased by single inhalation of low dose toluene (1700 ppm), but increased by repeated administration. At high blood toluene concentration, GABA levels were increased in all the brain areas assayed in this experiment and the increasing extents of inhibitory amino acid contents measured in caudate and hippocampus were greater than those of excitatory amino acids. These results suggest that the changes of amino acid neurotransmitter contents in brain by exposure to toluene may modulate toluene-induced behaviors.

• YAKHAK HOEJI
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• v.34 no.5
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• pp.323-333
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• 1990

To study influence of carbonmonoxide (CO) poisoning on the content of amino acid neurotransmitter in brain, male rat was exposed to CO 5000 ppm for 30 minutes (60-75% HbCO). Aspartic acid and glutamic acid level in the cerebral cortex and aspartic acid level in the striatum were significantly decreased. GABA level in the cerebral cortex was significantly increased after the 30 and 60 minutes of CO intoxication. Taurine level in both the cerebral cortex and the striatum was increased although nonsignificant. Consequently, the CO-induced hypoxia brain showed lower level of excitatory neurotransmitter, aspartic acid and glutamic acid and higher level of inhibitory neurotransmitter, GABA and taurine. These results suggest that the change in content of amino acid neurotransmitter in the rat brain may be concerned with several CO poisoning symptoms.

• The Korean Journal of Physiology and Pharmacology
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• v.3 no.1
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• pp.35-45
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• 1999

Excitatory amino acid (EAA) and substance P (SP) have been known to be primary candidates for nociceptive neurotransmitter in the spinal cord, and calcium ions are implicated in processing of the sensory informations mediated by EAA and SP in the spinal cord. In this study, we examined how $Ca^{2+}$ modified the responses of dorsal horn neurons to single or combined iontophoretical application of EAA and SP in the rat. All the LT cells tested responded to kainate, whereas about 55% of low threshold (LT) cells responded to iontophoretically applied NMDA. NMDA and kainate excited almost all wide dynamic range (WDR) cells. These NMDA- and kainate-induced WDR cell responses were augmented by iontophoretically applied EGTA, but suppressed by $Ca^{2+},\;Mn^{2+},$ verapamil and ${\omega}-conotoxin$ EVTA, effect of verapamil being more prominent and well sustained. $Ca^{2+}$ and $Mn^{2+}$ antagonized the augmenting effect of EGTA. On the other hand, prolonged spinal application of EGTA suppressed the response of WDR cell to NMDA. SP had triple effects on the spontaneous activity as well as NMDA-induced responses of WDR cells: excitation, inhibition and no change. EGTA augmented, but $Ca^{2+},\;Mn^{2+}$ and verapamil suppressed the increase in the NMDA-induced responses and spontaneous activities of WDR cells following iontophoretical application of SP. These results suggest that in the spinal cord, sensory informations mediated by single or combined action of EAA and SP can be modified by the change in calcium ion concentration.

• Proceedings of the PSK Conference
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• 2003.04a
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• pp.72-74
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• 2003

Excitatory amino acid (EAA) receptor, particularly NMDA receptor, are now known to be one of major transmitter receptors involved in synaptic excitation. Excessive release of EAA neurotransmitter, glutamate, is an important causative factor in the neurodegenerative processes and can cause neuronal damage and cell death. This excitotoxicity has been shown to be $Ca^{++}$ dependent. (omitted)

• Korean Journal of Biological Psychiatry
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• v.4 no.1
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• pp.136-145
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• 1997

We are report on three cases of typical clinical characterstics and treatment response in neuroleptic maligant syndrome(NMS), and reviewed the literatures of NMS. NMS was first recognized as a life-threatening complication of dopamine receptor antagonists, and defined as a catatonic-like states associated with fever, obtundation, muscle rigidity, and unstable vital sign in patients taking neuroleptic agents. Concepts of NMS have changed because medications other than classic neuroleptic drugs have been implicated as triggering agents and syndromes identical to NMS have been observed in other conditions. The important neurochemical features are probably functional dopamine deficiency and ensuing hyperactivity of excitatory amino acid neurotransmission in the basal ganglia and hypothalamus. Recognition of NMS and early discontinuation of neuroleptics are the most important step in its management. Supportive care includes management of hyperthermia and fluid replacement. Controversial therapeutic measures include the application of dopamine receptor agonists, excitatory amino acid antagonists, or dantrolene. Psychiatric patients with a history on NMS and psychotic relapse necessitating antipsycotics do not commonly redevelop NMS.

• The Korean Journal of Pharmacology
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• v.32 no.2
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• pp.283-292
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• 1996

The spinal dorsal horn is the area where primary afferent fibers terminate and cutaneous sensory information is processed. A number of putative neurotransmitter substances, including excitatory and inhibitory amino acids and peptides, are present in this region. In this study, single neurons of the spinal dorsal horn were acutely isolated and the properties of whole cell current and responses to excitatory and inhibitory neurotransmitters were studied by patch clamp technique. Transverse slice ($(300{\mu}m$) of lumbar spinal cords from young rats$(7{\sim}14\;days)$ were sequentially treated with two pretenses(pronase 0.75 mg/ml and thermolysin 0.75 mg/ml), then single neurons were mechanically dissociated. These neurons showed near-intact morphology such as multipolar, ellipsoidal and bipolar, and pyramidal cells and we recorded the typical whole cell currents of $K^+$, $Ca^{2+}$ and ligand-operated channels from these neurons. Glutamate $(30{\mu}M)$ and N-methyl-D-aspartate(NMDA, $30{\mu}M)$ induced inward currents of $117{\pm}12.4$ pA(n=5) and $49{\pm}6.9$ pA(n=3), respectively. Glycine $(1{\mu}M)$ potentiated glutamate-induced currents $4{\sim}5$ times and NMDA-induced currents $8{\sim}10$ times. In addition, glycine $(30{\mu}M)$ induced Inward current ($31{\pm}6.1$ nA, n=2), which was rapidly desensitized after the peak to a new steady-state level. However, the inward currents induced by ${\gamma}-amino$ butyric acid(GABA, $1{\mu}M$) decreased continuously after the peak($226{\pm}41.6$ pA, n=3) under the similar experimental condition. The ionic currents and pharmacological responses of isolated neurons in this work were similar to those observed in vivo or in vitro spinal cord slice, indicating that acutely isolated neurons could be effectively used for further pharmacological studies.