• 생약학회지
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• 제20권1호
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• pp.37-42
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• 1989

This study was carried out to investigate the effect of Glycyrrhizae Radix on serum corticosterone and blood histamine content by immobilization stress in mice. Corticosterone secretion and blood histamine level was significantly increased in mice by subjecting the animals to immobilization stress 1 hr. after intraperitoneal injection of Glycyrrhizae Radix extract (150 mg/kg) and glycyrrhizinic and (15 mg/kg). whereas, administration of cortisol $(7.5\;{\mu}g/kg)$ provoked a decrease in corticosterone secretion and histamine levels. These results suggested that glycyrrhizinic acid was effective on cortiosterone release provoked by immobilization stress and this release was mediated in part by histamine.

• The Korean Journal of Physiology and Pharmacology
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• 제18권1호
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• pp.41-46
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• 2014

The possible roles of spinal histamine receptors in the regulation of the blood glucose level were studied in ICR mice. Mice were intrathecally (i.t.) treated with histamine 1 (H1) receptor agonist (2-pyridylethylamine) or antagonist (cetirizine), histamine 2 (H2) receptor agonist (dimaprit) or antagonist (ranitidine), histamine 3 (H3) receptor agonist (${\alpha}$-methylhistamine) or antagonist (carcinine) and histamine 4 (H4) receptor agonist (VUF 8430) or antagonist (JNJ 7777120), and the blood glucose level was measured at 30, 60 and 120 min after i.t. administration. The i.t. injection with ${\alpha}$-methylhistamine, but not carcinine slightly caused an elevation of the blood glucose level. In addition, histamine H1, H2, and H4 receptor agonists and antagonists did not affect the blood glucose level. In D-glucose-fed model, i.t. pretreatment with cetirizine enhanced the blood glucose level, whereas 2-pyridylethylamine did not affect. The i.t. pretreatment with dimaprit, but not ranitidine, enhanced the blood glucose level in D-glucose-fed model. In addition, ${\alpha}$-methylhistamine, but not carcinine, slightly but significantly enhanced the blood glucose level D-glucose-fed model. Finally, i.t. pretreatment with JNJ 7777120, but not VUF 8430, slightly but significantly increased the blood glucose level. Although histamine receptors themselves located at the spinal cord do not exert any effect on the regulation of the blood glucose level, our results suggest that the activation of spinal histamine H2 receptors and the blockade of spinal histamine H1 or H3 receptors may play modulatory roles for up-regulation and down-regulation, respectively, of the blood glucose level in D-glucose fed model.

• 생약학회지
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• 제9권1호
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• pp.41-47
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• 1978

Total saponins and ether extracts of red and white ginseng were obtained and their effects on blood pressure in cat and their histamine liberating activities in rabbits were measured. 1) Ether extract of red ginseng showed a transient hypotensive effect and subsequently showed a remarkable and persistent hypotensive effect, whereas other three fractions, such as saponin fractions of red and white ginseng and ether extract of white ginseng showed only a initial transient hypotensive effects. 2) Histamine levels liberated into blood after administration of each fractions measured by the bioassay with guinea pig ileum. Ether extract of red ginseng immediately increased histamine contents in plasma but the histamine levels decreased to normal level within 10min in spite of decreased blood pressure was sustained. Although white ginseng saponin lowered blood pressure immediately when it is administered, histamine release was observed after 10min. The results suggest that hypotensive effects of ginseng seems to have no correlation with the histamine liberating activity. Ginseng appears to show hypotensive effect via some other mechanisms.

• The Korean Journal of Physiology
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• 제2권2호
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• pp.33-43
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• 1968

Histamine, 0.5 mg as histamine base in 4 ml of normal saline solution, was injected into rabbits anesthetized with nembutal and the mean blood pressure was kept in the range of $52{\sim}80\;mmHg$ for over one hour by supplemental additions. Following the injection of the test substances, 300 mg of urea and 200 mg of antipyrine intravenously, serial blood samples were obtained from the femoral artery and the internal jugular vein at $0.5{\sim}3$ minutes interval. The decreasing patterns in the concentrations of arterial and venous blood plasma samples were compared with each other. The ratio of the concentration of brain tissue to that of the final arterial plasma was also studied. By these measures the degrees of penetration of the test substances in the brain in the control and in the histamine treated rabbits were observed. The concentrations of antipyrine and urea in the arterial blood plasma were decreasing exponentially with respect to the time elapsed. The venous concentrations were anticipated to increase initially and to cross the arterial concentration curve in the point of equlibrium between the plasma and the tissue. On the contrary to the expectation venous concentration also revealed the decreasing tendency similar to that of arterial plasma. The similarity between these two curves, arterial and venous, would be atributable to the fact that the cerebral blood flow rate was large enough and the rising phase in the venous concentration curve was instantly over before serial blood samples were taken. Inspite of some similarity in the decreasing tedency in both concentration curves there were appreciable discrepancies between the arterial and venous plasma which would reflect the situation far from the equlibria among several compartments in the brain. Changes in plasma potassium levels caused by the injection of histamine or bleeding were observed, too. Using 8 rabbits as the control and 12 rabbits for the histamine treated group following results were obtained: 1. Both of the concentration curves, arterial and venous, declined rapidly at_first and slowly later on and approached same equilibrium concentration with the passage of time after a single injection. The time at which attained the same concentration was $2.0{\pm}0.54\;min.$ in the control and $4.3{\pm}1.92\;min.$ in the histamine treated group with respect to antipyrine. On the other hand in the case of urea they were $2.4{\pm}0.59\;min.$ in the control and $4.4{\pm}1.31\;min.$ in the histamine group, respectively. In the histamine treated group enlarged spaces for distribution of test substances were postulated. 2. The concentration of antipyrine in the brain tissue water revealed no significant differences between the control and experimental groups, showing $212{\pm}40.2\;mg/l$ in the control and $206{\pm}64.1\;mg/l$ in the histamine treated group. On the other hand urea revealed higher value in the histamine treated group than in the control, showing an enhanced penetration of urea into the tissue after injection of histamine. Urea concentration in the brain water was $32.3{\pm}3.36\;mg%$ in the control and $39.2{\pm}4.25\;mg%$ in the histamine treated group. 3. The distribution ratio of antipyrine in the brain tissue was very close to unity in the histamine treated animals as well as in the control. 4. The average of the distribution ratio of urea in the control animals was 0.77 and it showed the presence of blood-brain barrier with regard to urea. However in the histamine treated animals the distribution ratios climbed up to 0.86 and they were closer to unity than in the control animals. Out of 12 cases 5 were greater than 0.9 and 8 exceeded 0.85. It appeared that histamine enhanced the penetration of urea through the barrier. 5. Histamine injection and or hemorrhage caused an elevation of the concentration of potassium in plasma. In the event that histamine and hemorrhage were applied together the elevation of potassium exceed the elevation seen at the histamine alone. There was no evidence that the leakage of potassium from the brain tissue was dominant in comparison with the general leakage from the whole body.

• The Korean Journal of Physiology
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• 제2권2호
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• pp.21-31
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• 1968

The appearance rates of antipyrine and urea into cerebrospinal fluid from blood were studied in the rabbits which were in the state of hypotension and of high permeability in the capillary beds following injection of histamine. The alteration in the distribution of electrolytes among various compartments of the brain and the permeability characteristics in the blood-cerebrospinal fluid barrier were also observed. Adult male rabbits, weighing around 2 kg, were used. Twenty four rabbits were divided into 3 groups. Besides the control group, histamine treated rabbits were categorized into 2 groups. $H_1$ consisted of the rabbits showing moderate responses to histamine and ranging from 62 to 80 mmHg in their mean anterial blood pressure. The animals which belong to $H_2-group$ showed severe responses to histamine and the mean anterial blood pressures dropped to 30-50 mmHg. Animals were anesthetized with nembutal, 30mg/kg i.v. The mean arterial blood pressure was read by means of the mercury manometer connected to the femoral artery. The animals, treated with histamine, were kept in hypotensive state at least for 40 minutes before the administration of the test-substances. The test-substances, 300 mg of urea and 200 mg of antipyrine, were dissolved in 3 ml of distilled water and were injected into the ear vein of the rabbit. After 10 minutes elapsed arterial blood sample was taken from the femoral artery and cerebrospinal fluid from the cisterna magna. Brain tissues were also analysed with respect to electrolytes in order to observe the disturbances in the electrolytes balance as well as in the function of the central nervous system. The results obtained were as follow: 1. The ratio of antipyrine concentration in cerebrospinal fluid to that of arterial blood plasma, that was the distribution ratio, was close to unity, revealing a well established equilibrium between the compartments of blood and cerebrospinal fluid in 10 minutes. In other words, there was no diffusion barrier with regard to antipyrine. The ratios over unity which were frequently seen in the histamine treated animals were attributable to the early penetration of the substance into the cerebrospinal fluid. 2. The appearance rates of urea into the cerebrospinal fluid in the histamine treated rabbits were higher in comparison with those of in the control animals. The increasing tendency in the rates was particularly remarkable in the $H_2-group$, showing the enhanced penetration of urea across the boondary. 3. In the htisamine treated $H_2-group$ the concentration of potassium in the blood plasma and cerebrospinal fluid well exceeded the control values and showed 8.5 and 9.0 mEq/l in average, respectively. Simultaneous drops in the brain tissue water were noticed, suggesting the leakage of intracellular potassium. 4. There was a coincidence in the rising pattern of potassium in the blood plasma and in the cerebrospinal fluid of $H_2-group$ and at least partial removal of the blood-cerebrospinal fluid barrier with respect to potassium was suggested in these animals. 5. The concentration of sodium in the blood plasma or in the cerebrospinal fluid showed no significant changes following histamine injection. However, sodium in the brain tissue revealed slight elevation in the histamine treated groups. 6. The ratios of the concentrations of potassium to those of sodium, [K]/[Na] in the brain tissues, were 1.92 in the control 1.82 in the $H_1$ and 1.52 in the $H_2-group$, respectively. The marked drop in the $H_2-group$ might represent neural dysfunction in the extremely hypotensive rabbits.

• The Korean Journal of Physiology
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• 제9권1호
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• pp.33-37
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• 1975

Adult rabbits were anesthetized with nembutal, 30 mg/kg. Carotid artery and jugular vein were exposed surgically and cannulated with polyethylene tubing. Arterial blood pressure was recorded via pressure transducer on the physiograph and $100{\mu}g/ml$ of histamine solution was infused through the jugular vein by using the constant infusion pump with a rate of 0.92 ml/min or 1.40 ml/min. Mean arterial blood pressure was maintained at $40{\sim}70 mmHg$ and hypotension was kept for 2 hours. After the termination of this period, blood was taken and osmotic fragility was mea sured immediately. Also, every sample of normal blood and shocked blood was incubated for 1 hour or 2 hours at $37^{\circ}C$ in order to see whether or not there was some influence of incubation. Furthermore to clarify which component was responsible for the change on the fragility, the mixtures of normal blood cells with shocked plasma and shocked blood cells with normal plasma were also incubated at $37^{\circ}C$ for one or two hours and fragility in such cases was measured. The data obtained were analysed by probit-plot method and the concentration of saline solution at which the hemolysis started to occur, 50% of blood cells were hemolysed and that at which the red blood cells hemolysed completely were determined. The values for the blood of hypotension stage were compared with those of the control blood. The results obtained were as fellows: 1. Osmotic fragility of red blood cell was increased in hypotensive state induced by histamine. 2. The differences of osmotic fragility after two hours of incubation were negligible both in normal blood and in that of hypotensive state. 3. Osmotic resistance of normal red blood cell incubated in shock plasma was less than that of shock red blood cell incubated in normal plasma. It was suggested that plasma in hypotensive state caused by histamine might be primarily responsible for the alteration of red blood cell fragility.

• 한국산학기술학회논문지
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• 제14권12호
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• pp.6340-6345
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• 2013

본 연구는 열 자극으로 유도된 신경성 염증 상태에서 혈류량의 변화와 histamine의 치수혈류 조절에 관해 유기적 관계를 연구함으로써 치수혈류 조절기전을 밝히고자 하였다. 연구방법은 열 마리의 고양이를 전신마취 하에 사용되었으며, 치수혈류의 변화는 레이저 도플러 측정계(Periflux 4001, Stockholm, Sweden)을 사용하여 측정 하였다. 레이저 도플러 측정하는 프로브는 하악 견치의 치면에 위치하였다. 열 자극은 입력/출력 장치와 열 자극 제어 스크립트 파일을 사용하여 치아에 적용하였다. 열($40-65^{\circ}C$)에 따라 치수 혈류량이 증가를 확인하였으며, $55^{\circ}C$에서 가장 큰 변화가 나타났다. 열 자극의 변화가 없는 $45^{\circ}C$에서 Histamine($5{\mu}g/kg/1ml$)를 치아와 가까운 설 동맥으로 주입 시 열 자극만 처치한 그룹보다 현저한 증가가 나타났다. 본 연구는 열적 자극에 의해 발생된 신경성 염증상태에서 치수혈류 변화와 이에 히스타민의 기능적으로 관여함을 나타내주며, 치아 염증 상태의 기전을 밝힐 수 있는 가능성을 보여준다.

• Parasites, Hosts and Diseases
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• 제61권2호
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• pp.172-182
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• 2023

At the time of host attachment, ticks are very sensitive to histamine, but during rapid blood sucking they paradoxically require histamine. Using a rabbit model, we studied the effects of histamine and antihistamine during attachment and fast-feeding in different life stages of Haemaphysalis longicorns. We examined how they responded to histamine and antihistamine by analyzing the detachment rate, histology of feeding lesions, and post-feeding behavior. A significant difference (P<0.01) was found in the detachment rate between experimental and control treatments throughout the observation period. Ticks exhibited a higher detachment rate (30.1%) at 12 h after histamine application during attachment time and on antihistamine-treated skin (25.4%) at 96 h during fast-feeding. After feeding on histamine-treated rabbits, the fully engorged body weights of larvae and nymphs were 0.7±0.36 mg and 3.5±0.65 mg, respectively. An average increase in body weight of 0.6±0.05 mg and 3.2±0.30 mg was observed for larvae and nymphs compared to the respective control weights. Nymphs and adults engorged after antihistamine treatment had an average body weight of 1.3±0.54 mg and 54±0.81 mg, respectively. An average decrease in body weight was observed in antihistamine-treated H. longicornis compared with control nymphs (3.3±0.42 mg) and adults (174±1.78 mg). Skin biopsies were collected after treatment, and differential histopathological characteristics were found between the treatment and control groups. Tick-infested skin collected from rabbits in the antihistamine-treated group lacked erythrocytes in the feeding pool, indicating that antihistamine impaired tick fast-feeding stage.

• Parasites, Hosts and Diseases
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• 제56권1호
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• pp.53-59
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• 2018

Tick saliva is critically important for continuous attachment to the host, blood feeding for days, and transmission of tick-borne pathogens. To characterize the patterns of inflammatory cytokine gene expression during its attachment and blood sucking time, peripheral blood samples of rabbits infested with Haemaphysalis longicornis ticks were collected at different intervals. Blood histamine concentration was evaluated as well as gene encoding IFN-${\gamma}$, TNF-${\alpha}$, IL-2, IL-6, IL-4, and IL-10 were compared with non-infested rabbits. Blood histamine concentration of tick-infested rabbits during fast feeding time was significantly higher than that of non-infested rabbits. In both nymph and adult tick infested rabbits, expression of TNF-${\alpha}$ and IFN-${\gamma}$ genes were decreased significantly (P<0.05), while expression of IL-4, IL-6, and IL-10 were increased 1.3 to 7 folds in adult infested rabbits with the exception of IL-6 that was significantly (P<0.05) decreased in nymph infested rabbits. IL-2 was not expressed in either nymph or adult infestation. H. longicornis saliva is capable of modulate host responses through a complex correlation with histamine and Th1, Th2 mediated cytokines that suppress the inflammatory responses directed toward inflammatory mediators introduced into the host during tick feeding.

• The Korean Journal of Physiology
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• 제1권1호
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• pp.23-32
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• 1967

Disappearance rate of injected $D_2O$ from the arterial blood as well as the effect of histamine on the rate were studied in rabbits. The concentrations of $D_2O$ in the serial arterial samples obtained through a Polyethylene tubing inserted into the carotid artery were assayed by the freezing point elevation method of Reaser. At zero time 3 ml of isotonic $D_2O$ in normal saline was injected into the jugular vein and at the same time serial sampling of arterial blood started. The serial sampling interval was either 7.7 sec or 12.3 sec. In the histamine treated animals histamine diphosphate (0,5 mg of histamine base) was injected intravenously 30 minutes prior to the zero time. The following results were obtained. 1. $D_2O$ concentration in arterial plasma water, x, was empirically obtained by the sum of 2 exponential terms of time, $x=Ae^{-k1t}+Be^{-k2t},$ and its theoretical basis was sought. The first term of the right member of the equation was regarded to be attributable to the compartment P which possessed instantaneous exchange of water with plasma. The second term was postulated to represent the poorly exchangeable compartment. 2. The constant A of the equation was evaluated as 4,37% and 14.3% in the control and histamine treated groups, respectively. B was 1.19% in the control and 0.849% in histamine treated animals. 3. The disappearance rates determined were; $k_1=0.0519{\pm}0.0221\;sec^{-1}\;K_2=0.00454{\pm}0.00247\;sec^{-1}$ in the control group. $k_1=0.1137{\pm}0.0290\;sec^{-1}\;K_2=0.00499{\pm}0.00204\;sec^{-1}$ in the histamine group. 4. In the histamine treated animals the disappearance rate of the first term was larger than that of the control animals, suggesting an enlarged size of the rapidly exchangeable compartment with regard to the plasma water. On the other hand the constant B was decreased by histamine administration, suggesting a distribution of $D_2O$ in an enlarged volume. This view was also made clear by comparing the apparent asymptotes to which the concentration curves of $D_2O$ approached in respective groups. The asymptotes in the histamine treated group showed lower values.