• Biomolecules & Therapeutics
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• 제3권1호
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• pp.54-57
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• 1995

The effect of Ruthenium Red on the antinociceptive action of capsaicinoids was investigated using tail-flick test in mice. Capsaicin and KR-25018, when administered subcutaneously, had a potent antinociceptive effect against noxious heat stimulus. Ruthenium Red which is known to block the calcium channel coupled to the capsaicin receptor, when injected intraperitoneally more than 5 mg/kg, showed severe sedation and apparent antinociceptive effect against noxious heat stimulus. The 2.5 mg/kg Ruthenium Red, at which dose any significant sedative effect was not shown, had no effect on the antinociceptive effects of capsaicin and KR-25018. Considering this result, the antinociceptive effect of capsaicinoid may not be related to the Ruthenium Red sensitive calcium channel which is activated by capsaicin.

• 한국발생생물학회지:발생과생식
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• 제7권2호
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• pp.95-103
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• 2003

세포내 칼슘은 다양한 세포에서 중요한 생리적 반응을 일으키며, ruthenium red와 ryanodine은 중요한 칼슘 조절자로 작용한다. Ruthenium red는 세포내 칼슘 저장고에서의 calcium induced calcium release(CICR)를 저해한다. Ryanodine은 ryanodine 통로를 통한 칼슘 방출을 촉진한다. 본 실험은 두 조절자가 생쥐 난자와 초기배아의 세포내 칼슘이온 농도에 영향을 미치는지 여부와 그 유효농도를 알아보고자 수행하였다 난자 및 초기배아내 칼슘이온 함량 변화는 Fluo-3/AM을 이용하여 공초점 레이저주사 현미경을 사용하여 실시간으로 측정하였다. Ruthenium red는 고농도(30$\mu$M, 300$\mu$M)에서 난자와 초기배아의 세포내 칼슘이온 농도를 저하시켰고, ryandoine은 저농도(0.01$\mu$M)에서 세포내 칼슘이온 농도를 증가시켰지만 고농도(10$\mu$M)에서는 세포내 칼슘이온 농도를 감소시켰다. 본 실험결과를 보면, ruthenium red와 ryanodine은 생쥐의 난자 및 초기배아에서도 세포내 칼슘이온 농도에 영향을 미쳤고, 그 유효농도는 근세포를 포함한 체세포와는 차이가 있었다.

• Restorative Dentistry and Endodontics
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• 제19권2호
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• pp.621-632
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• 1994

This experiment was performed to study the effect of capsaicin on the excitatory amino acids (EAAs) neurotransmitter in medullary dorsal horn and to clarify the relationship between substance P and excitatory amino acids. Horizontal slice of rat medullary dorsal horn was prepared and perfused with modified Krebs-Ringer solution in brain slice chamber. Release of EAAs was induced by veratrine and capsaicin were added to perfusion solution to observe the changes in EAA release. Capsaicin and ruthenium red, capsaicin antagonist, were also systemically injected with 50mg/kg in first day and 100mg/kg in second day for 2 days. Medulla oblongata containing the medullary dorsal horn was isolated, homogenized and centrifused. Spernatant was freeze-dried and EAA was determined by HPLC. Release of glutamate and aspartate was significantly increased by veratrine or capsaicin, but veratrine evoked release of EAAs was blocked by capsaicin in vitro, and injected ruthenium red did not have effect on the contents of EMs in vivo. Systemically injected capsaicin evoked the slight decrease in content of glutamate and aspartate in medullary dorsal horn and this effect of capsaicin was unaffected by ruthenium red.

• Restorative Dentistry and Endodontics
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• 제20권2호
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• pp.423-431
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• 1995

Trigeminal spinal sensory nucleus is a main relay site in transmission of orofacial pain. Glutamate and aspartate playa role in transmission of primary afferents. This experiment was performed to study the role of capsaicin, KR-25018 and shogaol on the release of glutamate and aspartate from trigeminal spinal sensory nucleus. Release of excitatory amino acids(EAAs) was induced by electrical stimulation of oral mucosa with innocuous or noxious stimuli. Capsaicin($10{\mu}M$), KR-25018($10{\mu}M$), shogaol($10{\mu}M$), ruthenium red and capsazapine were added to perfusion solution to observe the changes in EAA release, and glutamate and aspartate were determined by HPLC. Release of glutamate and aspartate from trigeminal sensory nucleus was increased by noxious stimulation of oral mucosa, but innocuous stimulation did not affect on the release of EAA Capsaicin and KR-25018 increased the release of glutamate and aspartate, and effect of KR-25018 on release of EAA was more potent than capsaicin. But shogaol had a weak effect on release of EAA. Effect of capsaicin and KR-25018 was partially blocked by capsaicin antagonists, ruthenium red and capsazepine.

• 대한약리학회지
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• 제32권1호
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• pp.57-66
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• 1996

파충류 골격근의 근소포체에서 칼슘유리 채널의 존재를 밝히고저 뱀 골격근에서 근소포체를 분리하여 SDS-PAGE 전기영동, RyR의 정제, $[^3H]ryanodine$ 결합실험 및 $^{45}Ca$ 유리 실험으로 아래와 같은 결과를 얻었다. 1) 뱀골격근 소포체도 단일 band의 high molecular weight 단백을 가지고 있고, 그 mobility는 포유류 골격근의 것과 유사했다. 2) RyR의 정제과정에서 얻어진 $[^3H]ryanodine$의 peak 결합 분획에서 high molecular weight의 단백분획이 발견되었다. 3) 뱀 골격근 SR vesicles에 대한 $[^3H]ryanodine$의 maximum binding site와 Kd값은 각각 6.36 pmole/mg protein과 17.62nM이었으며, $[^3H]ryanodine$의 특이성 결합은 칼슘과 AMP에 의해 유의성있게 증가되었고 (P<0.005), tetracaine에 의해 억제되지 않았으나 ruthenium red와 $MgCl_2$에 의해 일부만 억제되었다. 4) 근 소포체로부터 $^{45}Ca$ 유리는 낮은 농도의 칼슘 $(1{\sim}10{\mu}M)$과 AMP에 의해 증가되었고 (P<0.05), 고농도의 칼슘 $(300{\mu}M)$, tetracaine, ruthenium red 또는 $MgCl_2$에 의해 억제되었다 (P<0.05). 이상의 실험성적으로 파충류 (뱀)의 골격근에도 칼슘유리 채별이 있어 근 수축시 세포내 칼슘 농도 조절에 관여할 수 있을 것으로 여겨지며, 채널의 기능적 특징 일부가 포유류의 것과 유사한 것으로 사료된다.

• Bulletin of the Korean Chemical Society
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• 제9권3호
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• pp.137-143
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• 1988

We have investigated the infrared spectra for carbon monoxide chemisorbed on silica supported ruthenium with and without potassium coating within the frequency range of 1800-2200 $cm^{-1}$ at various ruthenium concentrations and CO pressures. For the system without potassium coating, three bands were observed in the infrared spectra when CO was adsorbed on both the reduced and oxidized form of supported ruthenium. However, the relative intensities of these three bands were found to have no interdependence. Therefore, we have assigned each of these bands as arising from the CO stretching vibration for carbon monoxide molecules adsorbed on the Ru sites of different nature. On coating with potassium, the 2030 $cm^{-1}$ band observed for the system without potassium coating was found to suffer red shift by 10-30 $cm^{-1}$ and we conclude that this bathochromic shift is caused by enhancement in the capability of back donation of electrons from the metal atom to the antibonding ${\pi}{\ast}$ orbitals of CO due to the presence of potassium.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1993년도 제1회 추계심포지움 and 제2회 생리분자과학연구센터워크숍
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• pp.1-6
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• 1993

Capsaicin [N-(4-hydroxy-3-methoxybenzyl)-trans-8-methyl -6-nonenamide], a pungent principle of red pepper. is known to induce analgesia. Though it has shown remarkable pharmacological activity, the toxicity and side effects inhibited its wider application. The interest has been renewed by the emergence of its agonists, resineferatoxin and ruthenium red. Recently, few successful capsaicinoids including 01vanil (NE-19550), NE-28345, and NE-21610 were reported.

• The Korean Journal of Physiology and Pharmacology
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• 제15권1호
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• pp.53-59
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• 2011

The secretion of insulin from pancreatic ${\beta}$-cells is triggered by the influx of $Ca^{2+}$ through voltage-dependent $Ca^{2+}$ channels. The resulting elevation of intracellular calcium ($[Ca^{2+}]_i$) triggers additional $Ca^{2+}$ release from internal stores. Less well understood are the mechanisms involved in $Ca^{2+}$ mobilization from internal stores after activation of $Ca^{2+}$ influx. The mobilization process is known as calcium-induced calcium release (CICR). In this study, our goal was to investigate the existence of and the role of caffeine-sensitive ryanodine receptors (RyRs) in a rat pancreatic ${\beta}$-cell line, INS-1 cells. To measure cytosolic and stored $Ca^{2+}$, respectively, cultured INS-1 cells were loaded with fura-2/AM or furaptra/AM. $[Ca^{2+}]_i$ was repetitively increased by caffeine stimulation in normal $Ca^{2+}$ buffer. However, peak $[Ca^{2+}]_i$ was only observed after the first caffeine stimulation in $Ca^{2+}$ free buffer and this increase was markedly blocked by ruthenium red, a RyR blocker. KCl-induced elevations in $[Ca^{2+}]_i$ were reduced by pretreatment with ruthenium red, as well as by depletion of internal $Ca^{2+}$ stores using cyclopiazonic acid (CPA) or caffeine. Caffeine-induced $Ca^{2+}$ mobilization ceased after the internal stores were depleted by carbamylcholine (CCh) or CPA. In permeabilized INS-1 cells,$Ca^{2+}$ release from internal stores was activated by caffeine, $Ca^{2+}$, or ryanodine. Furthermore, ruthenium red completely blocked the CICR response in perrneabilized cells. RyRs were widely distributed throughout the intracellular compartment of INS-1 cells. These results suggest that caffeine-sensitive RyRs exist and modulate the CICR response from internal stores in INS-1 pancreatic ${\beta}$-cells.

• 대한약리학회지
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• 제31권2호
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• pp.207-217
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• 1995

To investigate the functional and immunological properties of the Ca-release channel in the sarcoplasmic reticulum(SR) of the eel skeletal muscle, $[^3H]ryanodine$ binding, SDS gel electrophoresis, $^{45}Ca\;release$ studies, and immunoblot assay were carried out in the SR of the eel skeletal muscle. Maximal binding sites(Bmax) and $K_D$ values of $[^3H]ryanodine$ for Ca-release channel of the SR of the eel skeletal muscle were $19.44{\pm}1.40\;pmole/mg$ protein and $15.55{\pm}1.69\;nM$, respectively. $[^3H]Ryanodine$ binding to RyR was increased by calcium and AMP. The SR of the eel skeletal muscle has two high molecular weight bands on the SDS PAGE. The mobility of upper band was more slower than the single band of the rabbit skeletal muscle, and that of the lower band was similar with the single band of canine cardiac muscle. Vesicular $^{45}Ca-release$ was activated by calcium. Ca-induced $^{45}Ca-release$ was significantly inhibited by $MgCl_2(2\;mM)$, ruthenium red$(10\;{/mu}M)$ or tetracaine(1 mM), but not by high concentration of calcium itself. AMP-induced $^{45}Ca-release$ was slightly occurred only in the absence of calcium, it was not inhibited by $MgCl_2$ or ruthenium red. Caffeine also increased $^{45}Ca-release$ from the SR vesicles, but it was not affected by $MgCl_2$ or ruthenium red. Polyclonal Ab against rat skeletal muscle RyR is reacted with that of rabbit, but not reacted with that of the eel skeletal muscle. These results suggested that ryanodine receptor of the SR of the eel skeletal muscle is showing some similar properties with that of mammalian skeletal muscle, but might be an another isotype channel having two bands which is less sensitive to AMP, not cross-reacted with antisera against rat RyR, and not inhibited by high concentration of calcium.

• 한국식품위생안전성학회지
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• 제9권3호
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• pp.163-168
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• 1994

In the present study we investigated the peripheral function of capsaicin and KR-25018, a newly synthesized capsaicin derivative, which was demonstrated to have a potent analgesic activity through different mechanism from morphine and nonsteroidal antiinflammatory drugs. Capsaicin (10-8~10-5 M) and KR-25018 (10-8~10-5 M) produced concentration-dependent contractions of the isolated guinea pig bronchi. There were no significant differences in the maximum response and the EC50 values (EC50: 0.137$\pm$0.025 $\mu$M and 0.097$\pm$0.031 $\mu$M for capsaicin and KR-25018, respectively, P>0.05). Phosphoramidon (10 $\mu$M) and indomethacin (10 $\mu$M) had no significant effect on contractile response to the submaximal concentration range of capsaicin and KR-25018 (3$\times$10-9~3$\times$10-7 M). The response to KR-25018, like that to capsaicin, was significantly inhibited by ruthenium red with reduction in the maximum response, which is indicative of non-competitive antagonism. A further common feature of the responses to capsaicin and KR-25018 in the guinea pig bronchi was their sensitivity to capsazepine. Capsazepine caused a rightward parallel shift in concentration-response curves obtained by capsaicin and KR-25018. the pA2 values of capsazepine were 5.90 and 5.99 against capsaicin and KR-25018 response, respectively. In conclusion, KR-25018 and capsaicin exert their contractile effects in the isolated guinea pig bronchial muscle by common mechanisms, probably via the activation of a specific receptor.