• 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.

• Journal of Applied Biological Chemistry
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• 제44권2호
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• pp.84-86
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• 2001

Capsaicin synthesis by suspension cultured cells of Jalapeno pepper (Capcicum annuum L.) was assessed in vitro under various conditions including temperature (23 and $30^{\circ}C$), light intensity (with light and without light), and shaking speed (110 and 200 rpm). Capsaicin production increased, while the cell biomass growth decreased possibly due to the production of a secondary metabolite. Capsaicin synthesis was primarily affected by light condition. Cells cultivated at 110 rpm and $23^{\circ}C$ under light condition yielded the highest fresh weight, while those cultivated under the same condition, but without light resulted in the lowest cell mass. Capsaicin content in cells of 18-day-old pepper grown at 110 rpm and $23^{\circ}C$ under light was 0.125% of the cell mass. However, without light treatment, the capsaicin content in cells at the same shaking speed and temperature increased up to 169%, indicating no light is favored in the capsaicin synthesis by Jalapeno pepper. Increasing the shaking speed from 110 to 200 rpm without light enhanced the capsaicin synthesis. Results of this study demonstrate that light condition is the limiting factor in the synthesis of capsaicin in tissue-cultured Jalapeno pepper cells.

• 약학회지
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• 제41권1호
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• pp.139-146
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• 1997

In the present study, capsaicin-induced desensitization of peripheral sensory nerves were investigated by using guinea pig bronchi, in which these nerves are stimulated with cap saicin to produce a contractile response via the release of sensory neuropeptides such as substance P and neurokinin A. The contractile response to capsaicin was inhibited by the combination of CP96345 and SR 48968 suggesting that the excitatory effect of capsaicin is mediated via both the tachykinin NK-1 and NK-2 receptor. Capsaicin produced in vitro-desensitization in dose-dependent manner, but after this in vitro-desensitization the response to NK-1 and NK-2 receptor agonist did not change. Systemic administration (s.c.) of capsaicin also desensitized significantly bronchial tissues but could not produce any change in the contractile response to the selective agonists of NK-1 and NK-2 receptor. Therefore, the present results suggest that functional desensitization to capsaicin-induced contractile response in guinea pig bronchi does not involve NK-1 and NK-2 receptor, while excitatory effect of capsaicin is mediated via both NK-1 and NK-2 receptor. In conclusion, it is suggested that capsaicin- induced excitation and desensitization involves somewhat different pathways.

• 약학회지
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• 제4권1호
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• pp.60-62
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• 1959

We found a fact, when Kochuzang goes on ferment, that capsaicin in Kochuzang breaks down to other substances. And those substances are less hot than original capsaicin. The degradation of capsaicin depends on the concentration of table salt in Kochuzang. Nevertheless, these is rather no difference between a Kochuzang which contains no salt and the other one which contains sufficient salt when we assay them by Electrophotometry. We can explain this contradiction by making an assumption that the degradation might be happened at the acid radical part of capsaicin and not at Vanillyl radical.

• 약학회지
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• 제38권1호
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• pp.12-19
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• 1994

Capsaicin(8-methyl-N-vanillyl-6-nonenamide) is the principal pungent component of Capsicum fruits. This work is directed to the capsaicin-hydrolyzing enzyme playing a key role in the rate limiting and critical step of capsaicin metabolism. In order to get precise information on the enzyme's subcellular location, rat liver homogenate was divided into six subcellular fractions by differential centrifugation technique: crude nuclear pellet, PNS(post nuclear supernatant) fraction, lysosomal pellet, cytosol, Tris wash fraction, micrisomes. Capsaicin-hydrolysing enzyme activity was analysed by high performance liquid chromatography(HPLC). This enzyme was found at the highest specific activity in the microsomal fraction and co-distributed with marker enzymes of the endoplasmic reticulum, NADPH-cytochrome c reductase and nucleoside diphosphatase. This is compatible with the result of ninhydrin color reaction of vanillylamine, primary metabolite of capsaicin hydrolysis, on thin layer chromatography(TLC). This enzyme is most active at pH $8.0{\sim}9.0$. Definite subcellular location of this enzyme will make it easy to proceed with further study.

• 한국환경성돌연변이발암원학회지
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• 제15권2호
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• pp.81-87
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• 1995

The clastogenic activity of capsaicin, a major pungent and irritating constituent of hot chili pepper, was evaluated in cultured human lymphocytes. Capsaicin (125, 250, and 500 $\mu$M) caused cytogenetic damage as determined by increased frequency of chromosome/chromatid aberrations compared to the solvent control. The mitotic indices were also decreased in a concentration-related manner in capsaicin-treated cells. Moreover, capsaicin suppressed [$^3$]thymidine incorporation into lymphocytes. The clastogenicity and cytotoxicity of capsaicin towards human lymphocytes were evident without an external metabolic activation system. Taken together, these findings suggest that capsaicin is a genotoxic agent and may thus represent a potential health hazard in humans.

• 약학회지
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• 제43권1호
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• pp.55-60
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• 1999

To investigate analgesic mechanism of capsaicin and its analogues (capaicinoids) adenosine release was measured by high performance liquid chromatography from rat spinal cord synaptosomes. Exposure of synaptosomes to $K^+$ and morphine produced a dose dependent release of adenosine in the presence of $Ca^{++}$. Capsaicin (0.1, 1, $10{\;}{\mu}M$), and its analogues: NE-19550 (1, 10, $100{\;}{\mu}M$), DMNE (1, 10, $100{\;}{\mu}M$) and KR 25018 (0.1, 1, $10{\;}{\mu}M$) produced a concentration dependent release of adenosine in the presence of $Ca^{++}$. Nifedifine, L-type voltage sensitive calcium channel blocker, inhibited $K^+$ (6, 12 mM)-and morphine ($10{\;}{\mu}M$)-evoked release of adenosine partially. Capsazepine, a novel capsaicin selective antagonist, blocked only capsaicin and capsaicinoids induced release of adenoside. Therefore, it is suggested that the adenosine release by capsaicin and capsaicinoids having antinociceptive effects involves actvation of capsaicin specific receptor and capsaicin sensitive $Ca^{++}$. channel.

• 대한약리학회지
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• 제29권1호
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• pp.33-41
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• 1993

Capsaicin의 중추신경계에 대한 진통효과를 척수 수준에서 규명하고, 이에 대한 norepinephrine (NE)계의 역할을 규명하기 위하여 tail flick reflex (TFR) latency time의 증가와 척수 내 NE 양의 변화를 측정하였다. 웅성의 Sprague-Dawley 백서를 pentobarbital sodium으로 마취를 하여 femoral vein cannulation과 intrathecal catheterization을 하였고, 이를 통하여 시험약제를 투여하였다. TFR은 capsaicin 또는 용매 투여전, 투여후 10분, 30분, 60분, 때로는 2시간에 측정하였다. MK-801은 capsaicin 투여전 20분에 femoral vein을 통하여 주입하였다. $35{\sim}150{\mu}g$의 capsaicin을 intrathecal로 주었을 때, TFR latency가 최고치인 7초를 넘어 정상인 2.9초에 비해 100% 이상의 증가를 보였고, 척수 내 NE은 16 ng/mg protein에서 7 ng/mg protein으로 50% 이상 감소하였다. 이와 같은 TFR latency의 증가와 NE의 감소는 전 실험기간 (capsaicin 투여후 2시간)에 걸쳐 관찰되었다. 반면, 50mg/kg의 capsaicin을 피하로 전신투여 하였을 경우에 척수 NE은 같은 변화를 보였으나 TFR latency의 차이는 없었다. 또한, 0.5 mg/kg의 MK-801를 i.v.로 전처치 하였을 때, intrathecal capsaicin에 의한 TFR latency의 증가와 척수 내 NE의 감소가 모두 억제되었다. 이상의 결과는 capsain이 excitatory aminoacid (EAA)계 - NE계 - 척수 dorsal horn으로 이루어진 동통전달의 하행성 억제계 축의 활성을 항진시켜 진통효과를 가져옴을 보여준다. 또한, capsaicin의 피하 주사시에 진통효과를 볼 수 없음을 말초 동통전달신경의 흥분에 의한 중추 동통전달계 환성의 촉진이 진통 효과를 상쇄함을 암시한다.

• 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.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1996년도 춘계학술대회
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• pp.252-252
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• 1996

We Investigated the peripheral excitatory effect of capsaicin and KR-25018, a newly synthesized capsaicin derivative which was demonstrated to have a potent analgesic activity. KR-25018 and capsaicin were found to be both potent efficacious contractors of isolated guinea pig bronchial smooth muscle. KR-25018 was equipotent with capsaicin and [Sar$\^$9/,Met(O$_2$)$\^$11/]-substance P, 10-fold more potent than histamine and 10-fold less potent than (${\beta}$ -Ala$\^$8/)-neurokinin A(4-10), and their -log(M)EC$\_$50/ values were 6.94${\pm}$0.08, 6.86${\pm}$0.05, 6.96${\pm}$0.07, 5.64${\pm}$0.04, 7.96${\pm}$0.02, respectively. Contractile responses to KR-25018 and capsaicin were potentiated by phosphoramidon (1 ${\mu}$M), an inhibitor of neuropeptide-inactivating endopeptidase, but completely abolished in a calcium-free medium. These responses to KR-25018 and capsaicin were unaffected by the NK-1 antagonist CP96345 (1${\mu}$M), partially inhibited by the NK-2 antagonist SR48968 (1 ${\mu}$M) but almost completely abolished by a combination of the antagonists. A vanilloid receptor antagonist capsazepine competitively antagonized the responses to both KR-25018 and capsaicin (pA$_2$: aganst KR-25018, 5.98${\pm}$0.47; against capsaicin, 5.80${\pm}$0.31), and a capsaicin-sensitive cation channel antagonist ruthenium red caused significant reduction in the maximum responses to KR-25018 and capsaicin (pD'$_2$: against KR-25018, 4.61${\pm}$0.33; against capsaicin 4.96${\pm}$0.21). In conclusion, the present results suggest that KR-25018 and cpasaicin act on the same vanilloid receptor inducing the influx of calcium through ruthenium red-sensitive cation channel and produce contractile responses via the release of tachykinins that act on both NK-1 and NK-2 receptor subtypes.