• The Korean Journal of Physiology and Pharmacology
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• 제18권5호
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• pp.377-381
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• 2014

Propofol is a widely used anesthetic. Many studies have shown that propofol has direct effects on blood vessels, but the precise mechanism is not fully understood. Secondary intrapulmonary artery rings from male rats were prepared and mounted in a Multi Myograph System. The following constrictors were used to induce contractions in isolated artery rings: high $K^+$ solution (60 mmol/L); U46619 solution (100 nmol/L); 5-hydroxytryptamine (5-HT; $3{\mu}mol/L$); or phenylephrine (Phe; $1{\mu}mol/L$). The relaxation effects of propofol were tested on high $K^+$ or U46619 precontracted rings. Propofol also was added to induce relaxation of rings preconstricted by U46619 after pretreatment with the nitric oxide synthase inhibitor $N^G$-nitro-L-arginine methyl ester (L-NAME). The effects of propofol on $Ca^{2+}$ influx via the L-type $Ca^{2+}$ channels were evaluated by examining contraction-dependent responses to $CaCl_2$ in the absence or presence of propofol (10 to $300{\mu}mol/L$). High $K^+$ solution and U46619 induced remarkable contractions of the rings, whereas contractions induced by 5-HT and Phe were weak. Propofol induced dose-dependent relaxation of artery rings precontracted by the high $K^+$ solution. Propofol also induced relaxation of rings precontracted by U46619 in an endothelium-independent way. Propofol at different concentrations significantly inhibited the $Ca^{2+}$-induced contractions of pulmonary rings exposed to high $K^+$-containing and $Ca^{2+}$-free solution in a dose-dependent manner. Propofol relaxed vessels precontracted by the high $K^+$ solution and U46619 in an endothelium-independent way. The mechanism for this effect may involve inhibition of calcium influx through voltage-operated calcium channels (VOCCs) and receptor-operated calcium channels (ROCCs).

• Journal of Korean Neurosurgical Society
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• 제54권1호
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• pp.1-7
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• 2013

Objective : This study was undertaken in the belief that the atypical antipsychotic drug quetiapine could prevent apoptosis in the penumbra region following ischemia, taking into account findings that show 5-hydroxytryptamine-2 receptor blockers can prevent apoptosis. Methods : We created 5 groups, each containing 6 animals. Nothing was done on the K-I group used for comparisons with the other groups to make sure adequate ischemia had been achieved. The K-II group was sacrificed on the 1st day after transient focal cerebral ischemia and the K-III group on the 3rd day. The D-I group was administered quetiapine following ischemia and sacrificed on the 1st day while the D-II group was administered quetiapine every day following the ischemia and sacrificed on the 3rd day. The samples were stained with the immunochemical TUNEL method and the number of apoptotic cells were counted. Results : There was a significant difference between the first and third day control groups (K-II/K-III : p=0.004) and this indicates that apoptotic cell death increases with time. This increase was not encountered in the drug groups (D-I/D-II : p=1.00). Statistical analysis of immunohistochemical data revealed that quetiapine decreased the apoptotic cell death that normally increased with time. Conclusion : Quetiapine is already in clinical use and is a safe drug, in contrast to many substances that are used to prevent ischemia and are not normally used clinically. Our results and the literature data indicate that quetiapine could help both as a neuronal protector and to resolve neuropsychiatric problems caused by the ischemia in cerebral ischemia cases.

• 약학회지
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• 제34권3호
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• pp.180-191
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• 1990

A comparison was made of the effects of selective ${\alpha_1}-adrenoceptor$ agonist phenylephrine and selective ${\alpha_2}-adrenoceptor$ agonist clonidine on endothelium-containing and endothelium-denuded rings of the rat aorta. In the case of phenylephrine, removal of endothelium increased sensitivity 2.5 fold at $EC_{50}$ level and maximum contractive response 1.4 fold. In the case of clonidine, which gave only 15% of maximum contractive response given to phenylephrine on endothelium-containing rings, removal of the endothelium increased sensitivity 5.6 fold at $EC_{50}$ level and maximum contractive response 5 fold, which was about 55% of that given by phenylephrine. In endothelium-denuded ring, phenylephrine-induced contraction tended to be more increased in tonic contraction than in phasic contraction as compared to that in endothelium-containing ring, while clonidine-induced contraction was monophasic and was increased only in tonic contraction. In the calcium-free solution or in the presence, of verapamil, contraction stimulated by clonidine was almost abolished while that stimulated by phenylephrine produced only phasic contraction. The depression of sensitivity to these agonists in rings with endothelium appeared to be due to the vasodepressor action of endothelium derived relaxing factor (EDRF), because hemoglobin, a specific blocking agent of EDRF, abolished this depression. It is unlikely that the endothelium-dependent relaxation was due to stimulation of release of EDRF, because clonidine did not produce endothelium-dependent relaxation in 5-hydroxytryptamine-precontracted ring even when its contractile action was blocked by the ${\alpha_1}-adrenoceptor$ antagonist, prazosin. When the efficacy of phenylephrine was reduced to about the initial efficacy of clonidine by pretreatment with dibenamine, the contraction-response curves for phenylephrine became very similar to the corresponding curves obtained for clonidine before receptor inactivation. In the dibenamine-treated rings, contraction of phenylephrine was abolished in calcium-free solution or in the presence of verapamil like that obtained for clonidine before receptor inactivation. These results suggest that EDRF spontaneously released from endothelium depress contraction more profoundly in a case of an agonist with low efficacy and the phenylephrine-induced contraction was totally dependent on extracellular calcium as was that obtained for clonidine when the efficacy of phenylephrine was reduced to that of clonidine by irreversible inactivation of ${\alpha_1}-adrenoceptor$ with dibenamine.

• Asian-Australasian Journal of Animal Sciences
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• 제32권3호
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• pp.341-349
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• 2019

Objective: Internal organs indirectly affect economic performance and well-being of animals. Study of internal organs during later layer period will allow full utilization of layer hens. Hence, we conducted a genome-wide association study (GWAS) to identify potential quantitative trait loci or genes that potentially contribute to internal organ weight. Methods: A total of 1,512 chickens originating from White Leghorn and Dongxiang Blue-Shelled chickens were genotyped using high-density Affymetrix 600 K single nucleotide polymorphism (SNP) array. We conducted a GWAS, linkage disequilibrium analysis, and heritability estimated based on SNP information by using GEMMA, Haploview and GCTA software. Results: Our results displayed that internal organ weights show moderate to high (0.283 to 0.640) heritability. Variance partitioned across chromosomes and chromosome lengths had a linear relationship for liver weight and gizzard weight ($R^2=0.493$, 0.753). A total of 23 highly significant SNPs that associated with all internal organ weights were mainly located on Gallus gallus autosome (GGA) 1 and GGA4. Six SNPs on GGA2 affected heart weight. After the final analysis, five top SNPs were in or near genes 5-Hydroxytryptamine receptor 2A, general transcription factor IIF polypeptide 2, WD repeat and FYVE domain containing 2, non-SMC condensin I complex subunit G, and sonic hedgehog, which were considered as candidate genes having a pervasive role in internal organ weights. Conclusion: Our findings provide an understanding of the underlying genetic architecture of internal organs and are beneficial in the selection of chickens.

• Journal of Pharmaceutical Investigation
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• 제30권3호
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• pp.213-218
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• 2000

Ondansetron is a potent, highly selective 5-hydroxytryptamine3(5-HT3) receptor- antagonist, for the management of nausea and vomiting induced by cytotoxic chemotherapy and radiography, and the treatment of post-operative nausea and vomiting. The purpose of the present study was to evaluate the bioequivalence of two ondansetron tablets, $Zofran^{TM}$, (Glaxo Wellcome Korea Ltd.) and Hana ondansetron (Hana Pharmaceutical Co., Ltd.), according to the guidelines of Korea Food and Drug Administration (KFDA). Eighteen normal male volunteers, $23.56{\pm}1.79$ year in age and $67.35{\pm}8.35\;kg$ in body weight, were divided into two groups and a randomized $2{\times}2$ cross-over study was employed. After one tablet containing 8 mg of ondansetron was orally administered, blood was taken at predetermined time intervals and the concentrations of ondansetron in serum were determined using HPLC with UV detector. Pharmacokinetic parameters such as $AUC_t,\;C_{max}\;and\;T_{max}$ were calculated and ANOVA test was utilized for the statistical analysis of the parameters. The results showed that the differences in $AUC_t,\;C_{max}\;and\;T_{max}$ between two tablets were 7.53%, -0.23% and -3.92%, respectively when calculated against the $Zofran^{TM}$, tablet. The powers $(1-{\beta})$ for $AUC_t,\;C_{max}\;and\;T_{max}$ were above 99.00%, above 99.00% and 84.99%, respectively. Minimum detectable differences $(\Delta)\;at\;{\alpha}=0.1\;and\;1-{\beta}=0.8$ were all less than 20% (e.g., 12.25%, 10.88% and 18.37% for $AUC_t,\;C_{max}\;and\;T_{max}$, respectively). The 90% confidence intervals were all within ${\pm}20%$ (e.g., $-0.70{\sim}15.76,\;-7.53{\sim}7.08\;and\;-16.27{\sim}8.42\;for\;AUC_t,\;C_{max}\;and\;T_{max}$, respectively). All of the above parameters met the criteria of KFDA for bioequivalence, indicating that Hana ondansetron tablet is bioequivalent to $Zofran^{TM}$, tablet.

• Journal of Ginseng Research
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• 제46권1호
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• pp.62-70
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• 2022

Background: Maternal Toxoplasma gondii (T. gondii) infection during pregnancy has been associated with various mental illnesses in the offspring. Ginsenoside Rh2 (GRh2) is a major bioactive compound obtained from ginseng that has an anti-T. gondii effect and attenuates microglial activation through toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB) signaling pathway. GRh2 also alleviated tumor-associated or lipopolysaccharide-induced depression. However, the effects and potential mechanisms of GRh2 on depression-like behavior in mouse offspring caused by maternal T. gondii infection during pregnancy have not been investigated. Methods: We examined GRh2 effects on the depression-like behavior in mouse offspring, caused by maternal T. gondii infection during pregnancy, by measuring depression-like behaviors and assaying parameters at the neuronal and molecular level. Results: We showed that GRh2 significantly improved behavioral measures: sucrose consumption, forced swim time and tail suspended immobility time of their offspring. These corresponded with increased tissue concentrations of 5-hydroxytryptamine and dopamine, and attenuated indoleamine 2,3-dioxygenase or enhanced tyrosine hydroxylase expression in the prefrontal cortex. GRh2 ameliorated neuronal damage in the prefrontal cortex. Molecular docking results revealed that GRh2 binds strongly to both TLR4 and high mobility group box 1 (HMGB1). Conclusion: This study demonstrated that GRh2 ameliorated the depression-like behavior in mouse offspring of maternal T. gondii infection during pregnancy by attenuating the excessive activation of microglia and neuroinflammation through the HMGB1/TLR4/NF-κB signaling pathway. It suggests that GRh2 could be considered a potential therapy in preventing and treating psychiatric disorders in the offspring mice of mothers with prenatal exposure to T. gondii infection.

• 대한약리학회지
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• 제25권1호
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• pp.1-11
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• 1989

혈압 및 심박동수 조절에 대한 serotonin성 기전의 역할을 흰쥐 뇌의 NTS에서 검토하고 catecholamine성 기전과 비교하여 다음과 같은 결과를 얻었다. 1) 5-HT를 NTS에 주사시 혈압 및 심박동수는 감소되었고, 5-HT 300 pmol을 NTS에 주사하였을 때 가장 현저하게 하강하였다. ${\alpha}-MNE$과 clonidine도 마찬가지로 혈압과 심박동수의 감소를 일으켰다. 5-HT의 효과는 5-HT 수용체 길항제인 ritanserin, methysergide 및 ketanserin의 전처치에 의하여 봉쇄되었다. 2) Reserpine과 6-OHDA를 전처치하였을 때는 5-HT에 의한 혈압 및 심박동수 감소가 현저하게 약화되었다. 3) 5,7-DHT 전처치 후에는 5-HT에 의한 혈압 및 심박동수 감소는 증가하였다. 한편 6-OHDA 전처치에 의하여서도 clonidine의 혈압 및 심박동수 감소 현상은 항진하였다. 4) 5,7-DHT와 6-OHDA를 i.c.v.로 전처치하였을 때 phenylephrine과 sodium nitropursside에 의한 압반사 감수성은 현저히 저하하였고, 이들을 NTS로 주사시도 압반사 감수성이 손상되었다. 5) Immunohistochemistry에 의해 NTS에서 catecholamine성 세포체, 신경축색 말단과 serotonin성 신경축색 말단을 관찰하였고, 6-OHDA 주사후에 catecholamine성 신경축색 말단의 varicosity는 현저히 감소하였다. 한편 5,7-DHT처치에 의하여서는 serotonin성 신경축색 말단의 varicosity가 현저히 감소하였다. 이상의 실험 결과, NTS에 있는 serotonin성 수용체의 활성에 의하여 (1) 혈압 및 심박동수 감소가 일어나며, (2) 이는 catecholamine성 신경계와 관련되어 야기되며, (3) serotonin과 catecholamine성 수용체는 NTS의 postsynaptic site에 존재하고, (4) serotonin과 catecholamine성 신경세포는 압반사 조절에 있어서 중요한 역할을 하는 것으로 사료된다.

• Tuberculosis and Respiratory Diseases
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• 제40권2호
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• pp.135-146
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• 1993

연구배경 : 급성 폐동맥색전증에서의 심폐기능 장애는 폐혈관계의 물리적 폐쇄와 신경체액성 반응에 의한 이차적인 기관지 및 혈관의 수축에 의하며, 혈소판에서 유리되는 serotonin이 체액성반응의 주 매개체인 것으로 알려져 있다. Positive End Expiratory Pressure(이하 PEEP 이라 칭함) 호흡요법은 성인성 호흡곤란증후군에서는 그 효과가 입증되어 널리 이용되고 있으나 폐동맥색전증에서의 역할은 아직 알려진 바 없다. 방법 : 연구자는 5-hydroxytryptamine 2 (이하 5-HT2라 칭함) 수용체의 선별 길항제인 ketanserin과 PEEP이 폐동맥색전증의 심폐기능 장애에 미치는 영향을 관찰하고 이들이 폐동맥색전증의 치료에 이용될 수 있을지를 검정해보기위해 한국산 잡견 13마리에 자가혈병을 이용하여 급성 폐동맥색전증을 일으킨후 대조군과 ketanserin 투여군, PEEP 적용군에서 환기 및 혈류역학의 제지표를 측정하여 다음과 같은 결과를 얻었다. 결과: 1) 폐동맥색전증을 일으키는데 사용된 혈병은 체중 Kg당 0.30~0.89($0.63{\pm}0.16$)gm 이었고 세 군간에 유의한 차이가 없었으며 평균 폐동맥압은 11~18($14{\pm}2$)mmHg 에서 색전증 유발 직후 38~46($42{\pm}2$)mmHg 까지 상승하였다. 2) 혈병 투여 30분후의 변화 혈병 투여 30분후 평균 폐동맥압 및 폐혈관저항은 증가하였고 심박출량은 감소하였으며, 동맥혈 산소분압과 산소운반량 및 혼합정맥혈 산소분압은 감소하였고 생리적 단락과 동맥혈 이산화탄소분압은 증가하였으며(p<0.05) 세 군간에 유의한 차이는 없었다. 대조군은 이후 실험기간중 상기 지표에 유의한 변화가 없었다. 3) Ketanserin 투여후의 변화 Ketanserin 투여후 대조군에 비해 평균 폐동맥압과 폐혈관저항은 낮았으며 심박출량은 높았고 생리적단락은 낮았으며 동맥혈 산소분압과 산소운반량은 높았다(p<0.05). 동맥혈 이산화탄소분압은 ketanserin 투여 30분후 감소하였다(p<0.05). 평균 전신동맥압은 ketanserin 122mmHg 에서 101mmHg로 하강하였고 한시간 후에는 투여전 수준으로 상승하였으며 통계적 유의성은 없었다. 혼합정맥혈 산소분압은 대조군에 비해 높은 경향을 보였으며 통계적 유의성은 없었다. 4) PEEP 적용군에서의 변화 PEEP 적용후 동맥혈 산소분압과 폐혈관저항은 증가하였고 심박출량은 감소하였으며 생리적 단락은 감소한 반면 산소운반량은 감소하였다(p<0.05). 한편 동맥혈 이산화탄소분압은 증가하였다(p<0.05). PEEP 제거후 평균 폐동맥압과 폐혈관저항은 감소해 대조군에 비해 낮았으며, 산소운반량과 심박출량은 증가해 대조군에 비해 높았다(p<0.05). 생리적단락은 대조군에 비해 낮았고(p<0.05) 동맥혈 이산화탄소분압은 감소해 대조군과 유의한 차이는 없었다. 혼합정맥혈 산소분압은 대조군에 비해 높았다(p<0.05). 5) 혈병 투여 4시간후 혈소판은 감소하였고 백혈구는 증가하였다(p<0.05). 결론 : 이상의 결과로 5-HT2 수용체의 선별 길항제인 ketanserin은 폐동맥색전증의 치료에 유용할 것으로 생각된다. 한편 PEEP용 적용증에는 혈류역학적 제지표가 악화되었으나 제거후에는 오히려 대조군에 비해 유의하게 호전되었으므로, 폐동맥색전증의 초기에 혈류역학적 상태가 허용되면 조심스럽게 단기간 적용해볼 수 있을 것으로 생각된다.