• The Korean Journal of Physiology and Pharmacology
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• 제6권5호
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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.

• 대한약리학회지
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• 제5권2호
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• pp.105-114
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• 1969

The author studied the action of autonomic drugs on the urinary bladder isolated from Ditrema temmincki Bleaker and the results obtained were summarized as follows: 1) The motility of the urinary bladder of the fish was stimulated by acetylcholine and physostigmine. The stimulating action of these drugs was antagonized by atropine. 2) The motility of the fish bladder was stimulated by epinephrine, nor-epinephrine and phenylephrine, but inhibited by isoproterenol. 3) The inhibitory effects of isoproterenol on the fish bladder was not affected by phenoxybenzamine, but blocked by propranolol. 4) The excitatory effects of phenylephrine on the fish bladder were blocked by phenoxybenzamine, but augmented by propranolol. 5) The excitatory effects of epinephrine and nor-epinephrine were reversed by phenoxybenzamine and augmented by propranolol. 6) The motility of the fish bladder pretreated with phenoxybenzamine and propranolol was not affected by isoproterenol, phenylephrine, epinephrine and nor-epinephrine. 7) It seemed that the bladder muscle of the fish had both alpha excitatory and beta inhibitory receptors. 8) The motility of the fish bladder was stimulated by nicotine and DMPP. The excitatory effects of these drugs were abolished by pretreatment with hexamethonium or atropine. 9) It is, therefore, concluded that there are ganglion cells furnished with cholinergic fiber in the bladder wall of the fish.

• The Korean Journal of Physiology
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• 제25권2호
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• pp.147-158
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• 1991

The effects of noradrenaline on the spontaneous contraction recorded from a strip of mucosa-free antral circular muscle were studied in the guinea-pig stomach, and the changes in slow waves and membrane resistance were analyzed in order to elucidate the mechanism for the excitatory response to noradrenaline. Electrical responses of circular muscle cells were recorded using glass microelectrodes filled with 3 M KCI. Electrotonic potentials were produced to estimate membrane resistance by the partition stimulating method. All experiments were performed in tris-buffered Tyrode solution which was aerated with 100% $O_2$ and kept at $35^{\circ}C$. The results obtained were as follows: 1) The spontaneous contractions were potentiated dose-dependently by the application of noradrenaline. 2) Through the experiments using adrenoceptor-blockers, the strong excitatory effect via $[\alpha}-adrenoceptors$ and the weak inhibitory efffect via ${\beta}-adrenoceptors$ were noted. 3) Noradrenaline produced hyperpolarization of membrane potential, and increases in the amplitude and the maximum rate of rise of slow waves. 4) In the presence of apamin, Ca-dependent K channel blocker, the characteristic hyperpolarization was not developed. However, the excitatory effect of noradrenaline on spontaneous contraction remained. 5) Membrane resistance was reduced during the hyperpolarized state by the application of noradrenaline, and the change of membrane resistance and the hyperpolarized state were completely abolished by apamin. From the above results, following conclusions could be made: Excitatory responses to noradrenaline result from the dominant ${\alpha}-excitatory$, and the weak ${\beta}-inhibitory$ action of noradrenaline. Hyperpolarization of membrane potential by noradrenaline is due to the activation of Ca-dependent K channel.

• 대한약리학회지
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• 제6권1호
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• pp.37-44
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• 1970

The author studied the actions of autonomic drugs on the uterine muscle isolated from Ditrema temmincki Bleeker, and the results obtained were summerized as follows. 1) The motility of the fish uterus was stimulated by epinephrine, norepinephrine and phenylephrine, but inhibited by isoproterenol. 2) The inhibitory effects of isoproterenol on the fish uterus was not affected by phenoxybenzamine, but blocked by propranolol. 3) The excitatory effects of phenylephrine on the fish uterus were blocked by phenoxybenzamine, but stimulated by propranolol. 4) The excitatory effects of epinephrine and norepinephrine were reversed by phenoxybenzamine and stimulated by propranolol. 5) The motility of the fish uterus pretreated with phenoxybenzamine and propranolol was not affected by isoproterenol, phenylephrine, epinephrine and norepinephrine. 6) It seemed that the uterine muscle of the fish had both alpha excitatory and beta inhibitory receptors. 7) The motility of the uterus of the fish was stimulated by acetylcholine. The stimulating action of acetylcholine was antagonized by atropine. 8) The motility of fish uterus was not affected by nicotine and DMPP. The actions of these drugs were not affected by pretreatment with hexamethonium and atropine. 9) It is, therefore, concluded that there are not present ganglia cells furnished with cholinergic fiber in the uterine wall of the fish.

• The Korean Journal of Physiology and Pharmacology
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• 제4권6호
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• pp.455-461
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• 2000

Zinc contained in the neurons of central nervous system is activity-dependently released and then attenuates NMDA (N-methyl-D-aspartate)-induced neurotoxicity while augmenting non-NMDA-induced neurodegeneration. Zinc also has been reported to produce antinociceptive action on the inflammation- and nerve injury-induced hyperalgesia in the behavioral test. In this study, we investigated the effects of zinc on the responses of dorsal horn cells to NMDA, kainate and graded electrical stimulation of C-fibers. In the majority of WDR cells (70.6%), zinc current-dependently inhibited WDR cell responses to NMDA and in the remaining cells, produced biphasic responses; excitation followed by inhibition. Zinc augmented the responses of WDR cells to iontophoretical application of kainate. The dominant effect of $Zn^{2+}$ on the responses of WDR cells to C-fiber stimulation was excitatory, but inhibition, excitation-inhibition and no change of the responses to C-fiber stimulation were induced. $Ca^{2+}-EDTA$ antagonized the excitatory or inhibitory effects of $Zn^{2+}$ on the WDR cell responses. These experimental findings suggest that $Zn^{2+}$ modulates the transmission of sensory information in the rat spinal cord.

• The Korean Journal of Physiology and Pharmacology
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• 제22권3호
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• pp.249-255
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• 2018

Echinacoside, an active compound in the herb Herba Cistanche, has been reported to inhibit glutamate release. In this study, we investigated the effects of echinacoside on spontaneous excitatory synaptic transmission changes induced by 4-aminopyridine (4-AP), by using the in vitro rat hippocampal slice technique and whole-cell patch clamp recordings from CA3 pyramidal neurons. Perfusion with echinacoside significantly suppressed the 4-AP-induced epileptiform activity in a concentration-dependent manner. Echinacoside reduced 4-AP-induced increase in frequency of spontaneous excitatory postsynaptic currents (sEPSCs) but it did not affect the amplitude of sEPSCs or glutamate-activated currents, implicating a presynaptic mechanism of action. Echinacoside also potently blocked sustained repetitive firing, which is a basic mechanism of antiepileptic drugs. These results suggest that echinacoside exerts an antiepileptic effect on hippocampal CA3 pyramidal neurons by simultaneously decreasing glutamate release and blocking abnormal firing synchronization. Accordingly, our study provides experimental evidence that echinacoside may represent an effective pharmacological agent for treating epilepsy.

• 대한약리학회지
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• 제5권1호
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• pp.29-33
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• 1969

The effects of Ginseng saponin on respiration and $Na^+$, $K^+$ content of rat cerebral cortex slices were investigated to determine the action of Ginseng saponin on brain cortex at cellular level. There are many reports for the study of Ginseng on central stimulatory action in experimental animals. The electrical stimulation of slices of cortex causes a loss of potassium. And the respiration is needed to maintain a supply of energy for active cation transport. The reduction in $Qo_2$ is a consequence of primary cessation of active cation transport. Ginseng saponin stimulated respiration which was depressed by Morphine. But there was no significant change of electrolyte. It is suggested that the Ginseng saponin act rather on metabolic process than neural excitatory mechanism in vitro.

• 대한본초학회지
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• 제20권2호
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• pp.115-125
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• 2005

Objectives : Polygalae Radix (PR) from Polygalae tenuifolia (Polygalaceae) has been clinically used as a sedative, anti-inflammatory, and anti-bacterial agent. To extend pharmacological effects of PR in the central nervous system (CNS) on the basis of its CNS protective effect, the present study was conducted to identify the effect of PR, whether it shows the neuroprotective action against excitatory neurotoxicity. Methods : To identify the protective effect of PR to excitatory neuro-toxic agent, the present study was focused on the PR effect on cell death, that was caused by applying NMDA to nerve cell, elevation of $(Ca^{2+})_i$, releasement of glutamate, and ROS generation. Result : 1. PR methanol extract, at the concentration range of 0.05 to 5 g/ml, significantly inhibited NMDA (1 mM)-induced neuronal cell death as well as MK-801 (non competitive NMDA antagonist). 2. PR methanol extract $(0.5\;{\mu}g/ml)$ inhibited NMDA (1 mM)-induced elevation of cytosolic calcium concentration $[Ca^{2+}]_i$. NMDA application in the presence of MK-801 $(10\;{\mu}M)$ failed to produce the increase of $[Ca^{2+}]_i$ through all the measurement time. 3. PR methanol extract $(0.5\;{\mu}g/ml)$ inhibited the NMDA-induced elevation of glutamate release. Also, MK-801 showed similar protective effects. 4. PR methanol extract $(0.5\;{\mu}g/ml)$ inhibited the NMDA-induced elevation of ROS generation. Also, MK-801 showed similar protective effects. Conclusion : The present study provides the availability of PR to exert its protective effect on the neuronal cell death in various neurodegenerative pathophysiological conditions.

• 동의생리병리학회지
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• 제21권2호
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• pp.432-437
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• 2007

Reactive oxygen species (ROS) are toxic agents that may be involved in various neurodegenerative diseases. Recent studies indicate that ROS are also involved in persistent pain through a spinal mechanism. In the present study, whole cell patch clamp recordings were carried out on substantia gelatinosa (SG) neurons in spinal cord slice of neonatal rats to investigate the effects of ROS on neuronal excitability and excitatory synaptic transmission. In current clamp condition, tert-buthyl hydroperoxide (t-BuOOH), an ROS donor, induced a electrical hyperexcitability during t-BuOOH wash-out followed by a brief inhibition of excitability in SG neurons. Application of t-BuOOH depolarized membrane potential of SG neurons and increased the neuronal firing frequencies evoked by depolarizing current pulses. Phenyl-N-tert-buthylnitrone (PBN), an ROS scavenger, antagonized t-BuOOH induced hyperexcitability. IN voltage clamp conditions, t-BuOOH increased the frequency and amplitude of spontaneous excitatory postsynaptic currents (sEPSCs). In order to determine the site of action of t-BuOOH, miniature excitatory postsynaptic currents (mEPSCs) were recorded. t-BuOOH increased the frequency and amplitude of mEPSCs, indicating that it may modulate the excitability of the SG neurons via pre- and postsynaptic actions. These data suggest that ROS generated by peripheral nerve injury can induce central sensitization in spinal cord.

• The Korean Journal of Physiology and Pharmacology
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• 제3권1호
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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.