• 약학회지
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• 제29권2호
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• pp.76-89
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• 1985

The effects of ginseng saponin on the activity, phosphorylation, [$^{3}$H] ouabain binding and light scattering (disruption) of purified $Na^{+}$ ,$K^{+}$ -ATPase isolated from the outer medulla of sheep kidney were compared to those of gypsophila saponin, sodium dodecylsulfate (SDS), and Triton X-100 on the same parameters. $Na^{+}$ , $K^{+}$ -ATPase activity, phosphorylation, and [$^{3}H$] ouabain binding were inhibited by ginseng saponin (triol>total>diol), SDS, or Triton X-100, but increased by gypsophila saponin. Low doses of ginseng saponin (3.mu.g saponin/.mu.g protein) decreased phosphorylation sites and ouabain binding site concentration (Bmax) without any change of turnover number and affinity for ouabain binding which were decreased by high dose of ginseng saponin (over 10.mu.g saponin/.mu.g protein), SDS or Triton X-100. On the other hand, gypsophila saponin increased the affinity without any change of Bmax for ouabain binding. Inhibition of $Na^{+}$ ,$K^{+}$ -ATPase activity by ginseng saponin and SDS or Triton X-100 appeared before and after decrease in light scattering, respectively. These data suggest that ginseng saponins (total, diol, triol saponin) inhibit $Na^{+}$ , $K^{+}$ -ATPase activity by specific direct and general detergent action at low and high concentrations, respectively, and this inhibitory action of ginseng sapornin to $Na^{+}$ , $K^{+}$ -ATPase is not general action of all saponins.

• The Korean Journal of Pain
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• 제35권3호
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• pp.261-270
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• 2022

Background: The rostral ventromedial medulla (RVM) is a critical region for the management of nociception. The RVM is also involved in learning and memory processes due to its relationship with the hippocampus. The purpose of the present study was to investigate the molecular mechanisms behind orexin-A signaling in the RVM and hippocampus's effects on capsaicin-induced pulpal nociception and cognitive impairments in rats. Methods: Capsaicin (100 g) was applied intradentally to male Wistar rats to induce inflammatory pulpal nociception. Orexin-A and an orexin-1 receptor antagonist (SB-334867) were then microinjected into the RVM. Immunoblotting and immunofluorescence staining were used to check the levels of cyclooxygenase-2 (COX-2) and brain-derived neurotrophic factor (BDNF) in the RVM and hippocampus. Results: Interdental capsaicin treatment resulted in nociceptive responses as well as a reduction in spatial learning and memory. Additionally, it resulted in decreased BDNF and increased COX-2 expression levels. Orexin-A administration (50 pmol/1 µL/rat) could reverse such molecular changes. SB-334867 microinjection (80 nM/1 µL/rat) suppressed orexin's effects. Conclusions: Orexin-A signaling in the RVM and hippocampus modulates capsaicin-induced pulpal nociception in male rats by increasing BDNF expression and decreasing COX-2 expression.

• 대한약리학회지
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• 제31권1호
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• pp.11-15
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• 1995

연수의 세로토닌 신경계는 내재성 하행성 동통 억제계 (endogenous descending pain inhibitory system) 에 있어서 중추적인 역할을 하고 있다. 연수의 세로토닌 신경세포에 대한 cholecystokinin (CCK) 및 second messenger systems에 작용하는 약물들의 작용을 알아보기 위하여, 쥐의 태자 (태생 14일) 로부터 연수를 분리하여 10동안 배양한 후 5-hydroxytryptamine (5-HT)의 분비에 대한 cholecystokinin (CCK) 및 second messenger systems에 작용하는 약물의 영향을 연구하였다. 배양 10일된 세포에 여러 neuropeptide들을 $10{\mu}M$ 농도로 48 시간동안 자극한 결과, CCK 와 substance P에 의하여 5-HT의 분비가 증가됨을 관찰하였다. Somatostatin, proctolin, thyrotropin releasing hormone, 및 interleukin-6 은 5-HT의 분비에 있어서 아무런 영향이 없었다. 어떠한 second messenger가 CCK에 의한 5-HT 분비에 연관되어 있나를 알아보기 위하여 calcium channel 봉쇄제인 nimodipine, 그리고 calmodulin 길항제인 calmidazolium의 영향을 살펴본 결과 nimodipine ($1{\mu}M$)은 거의 완전하게, 그리고 calmidazolium ($1{\mu}M$)은 부분적으로 유의하게 CCK에 의한 5-HT의 분비를 억제하였다. 또한 adenyl cyclase의 활성도를 높이는 forskolin ($5{\mu}M$)은 5-HT의 분비를 증가시켰지만 protein kinase C(PKC)를 활성화시키는 phorbol myristate acetate (PMA)는 $2{\mu}M$ 농도에서 5-HT의 분비에 아무런 영향을 미치지 아니하였다. 이상의 연구결과, calcium channel을 통한 calcium influx와 세포내 calmodulin이 CCK에 의한 5-HT분비 증가에 있어서 중요한 역할을 함을 제시한다. 또한, 5-HT의 분비에 있어서 cyclic AMP system이 중요한 역할을 하나, PKC system은 5-HT의 분비에 연관이 없음을 제시하고 있다.

• 한국임상수의학회지
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• 제22권3호
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• pp.186-189
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• 2005

초음파 히스토그램의 내부 장기에 대한 임상적용을 알아보기 위하여 다주파수 탐촉자의 초음파기기를 이용하여 실험하였다. 9마리의 정상 비글견을 우측전복부의 간과 우측신장, 좌측전복부의 간, 비장과 신장를 검사하였다. 같은 깊이의 B-모드 영상으로 간, 신장의 피질, 비장, 그리고 각 신장의 피질과 수질의 수치를 비교하였다. 우측신장피질의 메아리발생치는 간에 비하여 유의적으로 $15{\%}$ 낮았다. 비장의 메아리발생치는 좌측신장피질보다 $23{\%}$ 높았으며, 간은 좌측 신장피질보다 $30{\%}$ 높았다. 각 신장의 피질과 수질의 비교에서는 피질이 우측과 좌측에서 각각 $47{\%}$와 $65{\%}$ 높게 나타났다(P<0.05). 우측신장피질과 간실질간의 메아리발생치 비율은 $0.86{\pm}0.11$, 비장과 좌측신장간에는 $1.37{\pm}0.47$, 간실질과 좌측신장피질간에는 $1.30{\pm}0.19$이었으며, 이들 모두다 유의적인 차이가 있었다(p<0.05). 초음파 히스토그램은 간, 비장, 신장 같은 내장장기의 구조물의 초음파적 평가에서 정량적으로 평가하기에 단순하고 유용하고 실질적이다.

• The Korean Journal of Physiology
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• 제27권2호
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• pp.185-197
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• 1993

The rostral ventrolateral medulla (RVLM) includes vasopressor neurons, which transmit activation signals to the intermediolateral nucleus (IML) of the spinal cord, where the preganglionic sympathetic nucleus is located, to raise arterial blood pressure (BP). However, controversy exists as to the possible depressor area in the RVLM and the pathway involved. The present study persued evidence far the location of depressor neurons and the pathway by simultaneously observing changes in BP and the firing rate (FR) of cardiovascular neurons (CVNs) in the RVLM during the somatosympathetic reflex (SSR) elicited by peripheral nerve stimulation, since CVNs are known to contribute to the generation of the sympathetic nerve discharge. In 42 cats, anaesthetized with $\alpha-chloralose$, single unit recording was performed, using carbon filament electrodes inserted into the RVLM, enabling estimation of the post R wave unit histogram (PR-UNlT) and the spike triggered average of sympathetic nerve discharge (STA-SND), allowing identification of CVNs. Antidromic stimulation of spinal $T_2$ segment was followed to determine whether the identified CVN projects axonal endings to the spinal cord (reticulospinal neuron). The sciatic nerve was electrically stimulated at $A\delta-intensity$ (1 mA, 0.1 ms), 1 Hz and C-intensity (10 mA, 0.5 ms), 20 Hz to elicit the depressor, and pressor responses of the SSR, respectively. Simultaneous measurement of CVN firing rate was made. Experimental results are summarized as follows. 1) 20 out of 98 CVNs had axonal projections to the spinal cord and 17 out of 98 CVNs showed FR changes during SSR. 2) Response patterns of FR and BP during SSR were classified into 8 types. 3) These 8 different response patterns could be further classified into those from pressor and depressor neurons. These results demonstrate that some CVNs were identifiable as reticulospinal neurons responding to anti-dromic stimulation and that CVNs operating as depressor neurons as well as pressor neurons exist in the RVLM, both of which are involved with SSR mediation. Therefore, evidence was found that an independent depressor pathway might be involved in the mediation of SSR.

• The Korean Journal of Physiology and Pharmacology
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• 제19권2호
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• pp.159-165
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• 2015

Input signals originating from baroreceptors and vestibular receptors are integrated in the rostral ventrolateral medulla (RVLM) to maintain blood pressure during postural movement. The contribution of baroreceptors and vestibular receptors in the maintenance of blood pressure following hypotension were quantitatively analyzed by measuring phosphorylated extracellular regulated protein kinase (pERK) expression and glutamate release in the RVLM. The expression of pERK and glutamate release in the RVLM were measured in conscious rats that had undergone bilateral labyrinthectomy (BL) and/or sinoaortic denervation (SAD) following hypotension induced by a sodium nitroprusside (SNP) infusion. The expression of pERK was significantly increased in the RVLM in the control group following SNP infusion, and expression peaked 10 min after SNP infusion. The number of pERK positive neurons increased following SNP infusion in BL, SAD, and BL+SAD groups, although the increase was smaller than seen in the control group. The SAD group showed a relatively higher reduction in pERK expression when compared with the BL group. The level of glutamate release was significantly increased in the RVLM in control, BL, SAD groups following SNP infusion, and this peaked 10 min after SNP infusion. The SAD group showed a relatively higher reduction in glutamate release when compared with the BL group. These results suggest that the baroreceptors are more powerful in pERK expression and glutamate release in the RVLM following hypotension than the vestibular receptors, but the vestibular receptors still have an important role in the RVLM.

• The Korean Journal of Physiology and Pharmacology
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• 제7권4호
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• pp.231-238
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• 2003

The present study was undertaken to investigate the effect of bradykinin on secretion of catecholamines (CA) evoked by stimulation of cholinergic receptors and membrane depolarization from the isolated perfused model of the rat adrenal glands, and to elucidate its mechanism of action. Bradykinin $(3{\times}10^{-8}M)$ alone produced a weak secretory response of the CA. however, the perfusion with bradykinin $(3{\times}10^{-8}M)$ into an adrenal vein of the rat adrenal gland for 90 min enhanced markedly the secretory responses of CA evoked by ACh $(5.32{\times}10^{-3}M)$, excess $K^+$ ($5.6{\times}10^{-2}M$, a membrane depolarizer), DMPP ($10^{-4}$ M, a selective neuronal nicotinic agonist) and McN-A-343 ($10^{-4}$ M, a selective M1-muscarinic agonist). Moreover, bradykinin ($3{\times}10^{-8}$ M) in to an adrenal vein for 90 min also augmented the CA release evoked by BAY-K-8644, an activator of the dihydropyridine L-type $Ca^{2+}$ channels. However, in the presence of $(N-Methyl-D-Phe^7)$-bradykinin trifluoroacetate salt $(3{\times}10^{-8}M)$, an antagonist of $BK_2$-bradykinin receptor, bradykinin no longer enhanced the CA secretion evoked by Ach and high potassium whereas the pretreatment with Lys-$(des-Arg^9,\;Leu^9)$-bradykinin trifluoroacetate salt $(3{\times}10^{-8}M)$, an antagonist of $BK_1$-bradykinin receptor did fail to affect them. Furthermore, the perfusion with bradykinin $(3{\times}10^{-6}M)$ into an adrenal vein of the rabbit adrenal gland for 90 min enhanced markedly the secretory responses of CA evoked by excess $K^+$ $(5.6{\times}10^{-2}M)$. Collectively, these experimental results suggest that bradykinin enhances the CA secretion from the rat adrenal medulla evoked by cholinergic stimulation (both nicotininc and muscarinic receptors) and membrane depolarization through the activation of $B_2$-bradykinin receptors, not through $B_1$-bradykinin receptors. This facilitatory effect of bradykinin seems to be associated to the increased $Ca^{2+}$ influx through the activation of the dihydropyridine L-type $Ca^{2+}$ channels.

• The Korean Journal of Physiology and Pharmacology
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• 제8권5호
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• pp.265-272
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• 2004

The present study was attempted to investigate the effect of cilnidipine (FRC-8635), which is a newly synthesised novel dihydropyridine (DHP) type of organic $Ca^{2+}$ channel blockers, on secretion of catecholamines (CA) evoked by acetylcholine (ACh), high $K^+$, DMPP and McN-A-343 from the isolated perfused rat adrenal gland. Cilnidipine $(1{\sim}10{\mu}M)$ perfused into an adrenal vein for 60 min produced relatively dose- and time-dependent inhibition in CA secretory responses evoked by ACh $(5.32{\times}10^{-3}M),\;DMPP\;(10^{-4}M\;for\;2\;min)$ and McN-A-343 $(10^{-4}M\;for\;2\;min)$. However, lower dose of cilnidipine did not affect CA secretion by high $K^+\;(5.6{\times}10^{-2}\;M)$, higher dose of it reduced greatly CA secretion of high $K^{+}$. Cilnidipine itself did fail to affect basal catecholamine output. In the presence of cilnidipine $(10{\mu}M)$, the CA secretory responses evoked by Bay-K-8644 $(10{\mu}M)$, an activator of L-type $Ca^{2+}$ channels and cyclopiazonic acid $(10{\mu}M)$, an inhibitor of cytoplasmic $Ca^{2+}$-ATPase were also inhibited. Moreover, ${\omega}-conotoxin\;GVIA\;(1{\mu}M)$, a selective blocker of the N-type $Ca^{2+}$ channels, given into the adrenal gland for 60 min, also inhibited time-dependently CA secretory responses evoked by Ach, high $K^+$, DMPP, McN-A-343, Bay-K-8644 and cyclopiazonic acid. Taken together, these results demostrate that cilnidipine inhibits CA secretion evoked by stimulation of cholinergic (both nicotinic and muscarinic) receptors from the isolated perfused rat adrenal gland without affecting the basal release. However, at lower dose, cilnidipine did not affect CA release by membrane depolarization while at larger dose inhibited that. It seems likely that this inhibitory effect of cilnidipine is exerted by blocking both L- and N-type voltage-dependent $Ca^{2+}$ channels (VDCCs) on the rat adrenomedullary chromaffin cells, which is relevant to inhibition of both the $Ca^{2+}$ influx into the adrenal chromaffin cells and intracellular $Ca^{2+}$ release from the cytoplasmic store. It is thought that N-type VDCCs may play an important role in regulation of CA release from the rat adrenal medulla.

• 대한약리학회지
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• 제31권1호
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• pp.17-26
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• 1995

8주, 18주, 그리고 32주된 Spontaneously Hypertensive Rats (SHR)과 Wistar-Kyoto Rats(WKY)과의 blood pressure(혈압)를 측정하여본 결과 SHR 그룹이 WKY에 비해 19에서 70 mmHg 차이로 SHR 그룹이 WKY group에 비하여 혈압이 높았다. 18주된 SHR과 WKY에서 제 3 뇌실내 (intraventricular)로 투여된 morphine과 ${\beta}-endorphin$의 진통작용을 검색하여 보았다. WKY group에 비하여 SHR group에서 뇌실내로 투여된 ${\beta}-endorphin$은 진통작용에 있어서 상승작용 (potentiation)을 보임을 발견하였고 뇌실내로 투여된 morphine은 SHR group에서 약간만 상승작용을 보였다. SHR과 WKY group간에 opioid의 진통작용에 있어서 중요한 역할을 하는 Midbrain과 Medulla (pons), 그리고 spinal cord (척수)의 lumbar부위의 $[Met^5]-enkephalin$과 proenkep-halin A mRNA level을 측정하여 보았다. SHR과 WKY group간의 $[Met^5]-enkephalin$과 proenkephalin mRNA의 양은 별로 차이를 보이지 않았다. 이러한 결과로 미루어 볼때 SHR group에서 뇌실내로 투여된 ${\beta}-endorphin$은 그의 진통효과에 있어서 보인 상승작용은 척수상부에 위치하고 있는 opioid deptide의 양이 변해서가 아니라 다른 기전에 의하여 조절되어지고 있음을 시사한다.

• Applied Microscopy
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• 제30권3호
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• pp.265-272
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• 2000

낙지 Octopus minor의 상완 신경절을 광학현미경과 전자현미경을 통해 관찰한 결과 다음과 같은 결론을 얻었다. 낙지의 상완신경절은 각각의 흡반 밑에서 둥근 형태로 관찰되었는데 그들의 크기는 흡반의 크기에 비례하였다. 둥근 형태의 상완신경절은 피질부와 수질부 두 부분으로 구분되었던 바, 피질부에서는 신경세포의 집단이, 수질부에는 신경망이 위치해 있었다. 신경세포의 집단에서는 3종류(소, 중, 대형)의 신경세포들이 관찰되었는데 소신경세포는 직경이 $0.9{\mu}m$정도인 둥근 형태의 작은 세포인데 비해 중신경세포는 직경 $1.6\times1.3{\mu}m$정도인 타원형세포였다. 대신경세포는 직경이 $2.8{\mu}m$정도 크기의 난원형의 큰 세포로 확인되었고 이들 3종류의 세포들은 모두 전자밀도가 낮아서 밝게 관찰되었으며 세포소기관의 발달은 미진하였다. 또한 중신경세포인 경우에는 $0.6\times0.4{\mu}m$정도 크기의 전자밀도가 중등도인 방추형 신경교세포에 의해 둘러싸여 있었다. 수질부의 신경망에서는 다양한 크기의 수상돌기와 축색돌기들이 복잡한 그물형태를 하고 있었다. 이들은 돌기내에서 4종류의 화학연접소포 (chemical synaptic vesicle)들을 소지하고 있었는데, 전자밀도가 매우 높고 직경이 100 nm 정도인 electron-dense synaptic vesicle과 전자밀도가 중등도이며 직경이 90nm 정도인 median electron-dense synaptic vesicle 그리고 중앙에 전자밀도가 높은 둥근 핵을 포함하는 직경 90nm정도의 electron-dense cored synaptic vesicle등이 관찰되었다. 그러나 전자밀도가 투명한 연접소포(electron-lucent synaptic vesicle)는 직경이 50nm정도로 가장 작은 형태를 하고 있었다.