• Title/Summary/Keyword: and receptors

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Determination of Target Clean-up Level and Risk-Based Remediation Strategy (위해성에 근거한 정화목표 산정 및 복원전략 수립)

  • Ryu, Hye-Rim;Han, Joon-Kyoung;Nam, Kyoung-Phile
    • Journal of Soil and Groundwater Environment
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    • v.12 no.1
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    • pp.73-86
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    • 2007
  • Risk-based remediation strategy (RBRS) is a consistent decision-making process for the assessment and response to chemical release based on protecting human health and the environment. The decision-making process described integrates exposure and risk assessment practices with site assessment activities and remedial action selection to ensure that the chosen actions are protective of human health and the environment. The general sequences of events in Tier 1 is as follows: initial site assessment, development of conceptual site model with all exposure pathways, data collection on pollutants and receptors, and identification of risk-based screening level (RBSL). If site conditions do not meet RBSL, it needs further site-specific tier evaluation, Tier 2. In most cases, only limited number of exposure pathways, exposure scenarios, and chemicals of concern are considered the Tier 2 evaluation since many are eliminated from consideration during the Tier 1 evaluation. In spite of uncertainties due to the conservatism applied to risk calculations, limitation in site-specific data collections, and variables affecting the selection of target risk levels and exposure factors, RBRS provides us time- and cost-effectiveness of the remedial action. To ensure reliance of the results, the development team should consider land and resource use, cumulative risks, and additive effects. In addition, it is necessary to develop appropriate site assessment guideline and reliable toxicity assessment method, and to study on site-specific parameters and exposure parameters in Korea.

Modification of Endothelium on Contractile Response of Brain Vessels to Contracting Agents (혈관 수축제의 뇌혈관 수축반응에 대한 혈관근 내피세포의 역할)

  • Kook, Young-Johng;Baik, Yung-Hong;Kim, Jong-Keun;Choi, Bong-Kyu;Choi, Soo-Hyung;Kim, Yung-In
    • The Korean Journal of Pharmacology
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    • v.24 no.2
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    • pp.203-216
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    • 1988
  • To delineate the mechanisms of vasoconstriction and vasodilation in cerebral arteries the effects of some vasoconstrictors and calcium antagonists on the basilar artery (BA) and arterial circle of Willis (WC) were examined and also the role of endothelium in the action of these drugs was investigated in pigs, cats and rabbits. In pig cerebral arteries, dose-dependent contractile responses were elicited by KCI, histamine, 5-hydroxytryptamine (5-HT) and angiotensin, but norepinephrine (NE), phenylephrine (PE) and epinephrine (EP) elicited dose-dependent contractions only under pretreatment with propranolol 10-6 M. The magnitudes of maximal contractile effects of these drugs were different from each other, and 5-H~ was the largest and angiotensin the smallest. Some calcium antagonists dose-dependently inhibited KCI (35 mM)-induced contraction and the order of potency in inhibiting the contraction was nifedipine > > diltiazem > flunarizine > oxybutynin > isosorbide dinitrate (ISDN) > glyceryl trinitrate. 5-HT (10-6 M)-induced contraction was dosedependently inhibited by nifedipine but slightly inhibited by diltiazem and ISDN. In rings with intact endothelium, KCI (35 mM)-induced contraction was not affected by acetylcholine (ACh) but $PGF_{2{\alpha}}$ (lO-SM)-induced contraction was dose-dependently relaxed by ACh and adenosine. This endothelium-dependent relaxation was not affected by nifedipine (l0-6M)-pretreatment but markedly inhibited by methylene blue (50,uM)-pretreatment. In the porcine arterial rings without endothelium, ACh had no effect or even contracted the $PGF_{2{\alpha}}-induced$ contraction. However, the dosedependent relaxing effect of ACh appeared when the deendothelized porcine ring and rabbit thoracic aorta with intact endotheli urn were simultaneously suspended into a bath and this relaxing effect was also inhibited by methylene blue-pretreatment. In cat cerebral arteries, 5-HT and NE elicited dose-dependent contractile responses and ACh also produced dose-dependent contraction regardless of the existence of endothelium. ACh-induced contraction was most prominent. 5-HT (IO-SM)induced contraction was not relaxed but contracted additionally by ACh even in the intact endothelial ring. In rabbit cerebral arteries, 5-HT and NE elicited dose-dependent contractile responses and 5-HT-induced contraction was more prominent. In the intact endothelial preparations, 5-HT (lO-s M)-induced contraction was markedly relaxed by the addition of ACh( IO-SM) and this endothelium-dependent relaxing effect was inhibited by atropine (l0-7M)-pretreatment but notaffected by diltiazem (l0-6M)-pretreatment. These results suggest that ACh elicits endotheliumdependent relaxing effect mediated by muscarinic receptors in cerebral arteries of pig and rabbit, and that ACh acts as vasoconstrictor in cat cerebral artery.

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Effect of the magnetism(neodymium magnet) on growth factor receptors of osteoblasts (희토류 자석의 자성이 골모세포 성장인자 수용체의 증가에 미치는 영향에 관한 연구)

  • Lee, Sang-Min;Lee, Sung-Bok;Choi, Boo-Byung
    • Journal of Dental Rehabilitation and Applied Science
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    • v.19 no.2
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    • pp.87-96
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    • 2003
  • The purposes of this study were to find out the optimum intensity of magnetic field where magnetism could promote the activity of osteoblast, and to discover the possibility of clinical application in the areas of dental implants and bone grafts by confirming the effect of clinically increasing bone formation. In this experiment, we used the Neodymium magnet, which had magnetic power six times as strong as the current ones and enabled the resistances against the demagnetization up to 20 to 50 times to be minimized with the size of 1mm in sight. In order to culture cells, a specially designed device was used. It was made to adjust the distance and accordingly to control the intensity of the magnetic field, by placing the cell culture plate in the center with a magnet of 1mm long and thick installed on the both ends. Using MC3T3-E1 cell, a kind of osteoblast-like cell, we cultured, for 24 hours, not only the test group which had been cultured under the magnetic fields with different intensity of 5, 10, 50, 100, 500, and 1000 Gauss, but also the control group excluding the influences of the magnetic field. After observing the cell's form and the density of the culture medium through an inverted microscope, we made a series of proceedings needed for the immunofluoroscence staining, such as fixation, normal serum reaction, primary antibody reaction, and secondary antibody reaction. And with a fluorescence microscope, we observed those-above and compared the frequency of expression of IFG-1 receptor. To make a Western immunoblotting analysis, the cells cultured under the same condition as the above had the procedure of the lysis buffer and the acrylamide gel electrophoresis was carried out. Protein transferred into the nitrocellulose membrane and tested on the primary and the secondary antibody reactions was observed and compared. The results were as follows: When observed through an inverted microscope, the nuclear divisions of the cells under the magnetic field of 10 Gauss were the most active, and the density of the cells could be observed the most enormously. As the result of an immunofluoroscence staining of IGF-1 receptor, the expression of IFG-1 was the most frequently observed under the magnetic field of 10 Gauss. On the other hand, few differences of consideration were made between the test group cultured under the magnetic fields of 5, 500, and 1000 Gauss and the control group. In respect of the expression of IFG-1 receptor, the test group cultured under the magnetic fields of 50 and 100 Gauss were higher than the control group, and lower than that cultured under the magnetic field of 10 Gauss.(p<0.05) According to the Western immunoblotting analysis, the band of IFG-1 receptor which had 85KDa of molecular weight was the darkest. Judging from the above-mentioned results, the growth factor receptor of an osteoblast cell which was an important criterion for the bone formation was increased in maximum under the magnetic field of 10 Gauss. Moreover it was observed that the optimum intensity of magnetic field in which magnetism made the activity of the osteoblast cell increase was about 10 Gauss.

Effects and Molecular Mechanisms of Eupatorium chinensis var. simplicifolium Extract on Abnormal Proliferation of Vascular Smooth Muscle Cells (등골나물추출물의 혈관 평활근 세포의 비정상 증식에 대한 억제 효과 및 분자기작)

  • Kim, Min-Jeong;Kim, Jihee;Lee, Jin-Ho;Kim, Minah;Woo, Keunjung;Kim, Han Sung;Kim, Tack-Joong
    • Journal of Life Science
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    • v.31 no.9
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    • pp.787-795
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    • 2021
  • Eupatorium chinensis var. simplicifolium (EUC) has anti-inflammatory and antioxidant effects. Young sprouts of EUC have been used as food for a long time, and the whole EUC plant has been used as an herbal remedy in oriental medicine. Arteriosclerosis, or chronic inflammation in arterial vessels, is a cardiovascular disease and is involved in various disorders. Cardiovascular diseases such as restenosis and neuropathic hyperplasia are mainly caused by abnormal growth and movement due to multiple growth factors in vascular smooth muscle cells (VSMCs). Platelet-derived growth factor (PDGF) is a mitogen released from damaged vessel walls and is involved in the proliferation and migration of VSMCs. To determine the effects of EUC on the abnormal proliferation and migration of VSMCs, the present study investigated intracellular signaling pathways in PDGF-BB-induced VSMCs treated with and without EUC. Pretreating PDGF-BB-induced VSMCs with EUC tended to effectively decrease cell proliferation and migration. Subsequently, the intracellular growth-related signaling pathways of AKT, phospholipase C gamma (PLC-γ), and mitogen-activated protein kinase (MAPK) were investigated using western blotting to confirm inhibited phosphorylation. Furthermore, flow cytometry data showed that EUC blocked the cell cycle of VSMCs. These results suggest that EUC can inhibit the proliferation and migration of VSMCs by controlling the cell cycle and growth factor receptors. Furthermore, this indicates that EUC can be used as a preventative against cardiovascular disease resulting from abnormal proliferation and migration of VSMCs.

Comparison of Human Health Risk Assessment of Heavy Metal Contamination from Two Abandoned Metal Mines Using Metal Mine-specific Exposure Parameters (국내 폐금속 광산에 특화된 노출인자를 이용한 두 폐금속 광산 중금속 오염에 대한 인체위해성평가 비교)

  • Lim, Tae-Yong;Lee, Sang-Woo;Cho, Hyen Goo;Kim, Soon-Oh
    • Journal of Environmental Impact Assessment
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    • v.25 no.6
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    • pp.414-431
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    • 2016
  • There are numerous closed and abandoned mines in Korea, from which diverse heavy metals (e.g., As, Cd, Cu, Pb, Zn) are released into the surrounding soil, groundwater, surface water, and crops, potentially resulting in detrimental effects on the health of nearby residents. Therefore, we performed human risk assessments of two abandoned metal mines, Yanggok (YG) and Samsanjeil (SJ). The exposure parameters used in this assessment were specific to residents near mines and the included exposure pathways were relevant to areas around metal mines. The computed total excess carcinogenic risks for both areas exceeded the acceptable carcinogenic risk ($1{\times}10^{-6}$), indicating that these areas are likely unsafe due to a carcinogenic hazard. In contrast, the non-carcinogenic risks of the two areas differed among the studied receptors. The hazard indices were higher than the unit risk (=1.0) for male and female adults in YG and male adults in SJ, suggesting that there are non-carcinogenic risks for these groups in the study areas. However, the hazard indices for children in YG and female adults and children in SJ were lower than the unit risk. Consumption of groundwater and crops grown in the area were identified as major exposure pathways for carcinogenic and non-carcinogenic hazards in both areas. Finally, the dominant metals contributing to carcinogenic and non-carcinogenic risks were As and As, Cu, and Pb, respectively. In addition, the carcinogenic and non-carcinogenic risks of YG were evaluated to be 10 and 4 times higher than those of SJ, respectively, resulted from the relatively higher exposure concentration of As in groundwater within SJ area. Because of lacking of several exposure parameters, some of average daily dose (ADD) could not be computed in this study. Furthermore, it is likely that the ADDs of crop-intake pathway included some errors because they were calculated using soil exposure concentrations and bioconcentration factor (BCF) rather than using crop exposure concentrations.

Relationship between Gb3 Expression and Cytotoxicity of Shiga-like Toxin I (Shiga-like Toxin I의 세포독성과 수용체 Gb3 발현과의 관계)

  • Lim, Suk-Hwan;Kim, Gi-Young;Kim, Hyung-Chun;Kim, Young-Hee;Son, Yong-Hae;Oh, Yang-Hyo;Park, Yeong-Min
    • Clinical and Experimental Pediatrics
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    • v.46 no.2
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    • pp.143-153
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    • 2003
  • Purpose : Infection with Shiga-like toxin (SLT)-producing Escherichia coli, an emerging human pathogen found particularly in young children under 5 years of age, causes a spectrum of illnesses with high morbidity and mortality, ranging from diarrhea to hemorrhagic colitis and hemolytic uremic syndrome. Host mediators play an important role in the pathogenesis of SLT-I toxicity. The experiments described here were designed to investigate the effect of SLT-I on TNF-${\alpha}$ production and to understand the effect of TNF-${\alpha}$ on GB3 expression. We also further examine the relationship between the Gb3 level and the differential susceptibility of cells to the cytotoxic action of SLT-I. Methods : The effect of purified SLT-1 from E. coli O157 : H7 (ATCC 43890) on tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) production in Raw264.7 cells was investigated. Many mediators regulate endothelial cell membrane expression of the glycolipid globotriaosyleramide (Gb3), which serves as the toxin receptor, suggesting that the host response to the toxin or other bacterial products may contribute to pathogenesis by regulating target cell sensitivity to the toxins. Therefore, the relationships between Gb3 expression and cytotoxicity against SLT-I on three types of cells were evaluated. Results : Detectable levels of TNF-${\alpha}$ were produced as early as six hours after induction and continued to increase during 48 hours by SLT-I. It was also found that Vero cells and dendritic cells (DC2.4 cells) expressed high levels of Gb3, 83% and 68%, respectively, and that Raw264.7 cells had a low level of Gb3 (29%) and appeared refractory to cytotoxicity against SLT-I. Vero cells and DC2.4 cells expressing high levels of Gb3 were highly susceptible to SLT-I. Furthermore, macrophages showed a resistance to SLT-I cytotoxicity, despite the fact that Gb3 expression was enhanced. Conclusion : These results strongly suggest that the expression of Gb3 is necessary but not sufficient to confer sensitivity of macrophages to SLT-I and further underpin the important role of SLT-I and its Gb3 receptors in the pathogenesis of E. coli O157 infection.

Effect of Lead Acetate on Pancreatico-biliary Secretion (납(Lead)이 취외분비 기능에 미치는 영향)

  • Sheen, Yhun-Yhong;Kim, Won-Joon
    • The Korean Journal of Pharmacology
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    • v.17 no.1 s.28
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    • pp.17-25
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    • 1981
  • No evidence has accumulated that lead compound is an essential component for biological function in animals. Lead is absorbed primarily through the epithelial mucosal cells in duodenum and the absorption can be enhanced by the substances which bind lead and increase its solubility. Iron, zinc and calcium ions, however, decrease the absorption of lead without affecting its solubility, probably by competing for shared absorptive receptors in the intestinal mucosa. Therefore, the absorption of lead is increased in iron deficient animals. Lead shows a strong affinity for ligands such as phosphate, cysteinyl and histidyl side chains of proteins, pterins and porphyrins. Hence lead can act on various active sites of enzymes, inhibiting the enzymes which has functional sulfhydryl groups. lead inhibits the activity of ${\delta}$-aminolevulinic acid dehydratase for the biosynthesis of hemoproteins and cytochrome, which catalyzed the synthesis of monopyrrole prophobilinogen from ${\delta}$-aminolevulinic acid. Accordingly lead decrease hepatic cytochrome p-450 content, resulting an inhibition of the activity of demethylase and hydroxylase in liver. Little informations are available on the effect of lead on digestive system although the catastrophic effects of lead intoxication are well documented. The present study was, therefore, attempted to investigate the effect of lead on pancreaticobiliary secretion in rats. Albino rats of both sexes weighing $170{\sim}230g$ were used for this study. The animals were divided into one control and three treated groups, i.e., control (physiologic saline 1.5ml/kg i.p.), lead acetate $(l0{\mu}mole/kg/day\;i.p.)$, $Pb(Ac)_2$ and EDTA$(each\;10{\mu}mole/kg/day\;i.p.)$, $Pb(Ac)_2$ and $FeSO_4(each\;l0{\mu}mole/kg/day\;hp)$. The pancreatico-biliary juice was collected under urethane anesthesia, and activities of amylase and lipase were determined by employing Sumner's and Cherry and Crandall's methods. The summarized results are follows. 1) In the experiment for acute toxicity of lead acetate, 20% of mortality was observed in rat treated with lead acetate as well as inhibition of the activity of amylase in the juice at the 3 rd day of the treatment. 2) No increases in body weight were observed in rats treated with lead acetate, while in control group the significant increases were observed. However, the body weights of animals were increased in the group lead acetate plus EDTA or $FeSO_4$. 3) Lead acetate decreased significantly the volume of pancreatico-biliary juice whereas additional treatment of EDTA and $FeSO_4$ prevented it. 4) Total activity of amylase was markedly reduced due to lead acetate treatment, but no change was showed following additional treatment with EDTA and $FeSO_4$. 5) No changes in the cholate and lipase output were observed in rats treated with lead acetate as compared with that of control rats. 6) Increase in bilirubin output in rats treated with lead acetate was shown on the 2nd and 3rd weeks treatment. 7) In the case of in vitro experiment, lead acetate also markedly inhibited release of amylase from pancreatic fragment. 8) Histologic finding indicated that acini vacuolation was induced in the pancreatic tissue of rat treated with lead acete. From the above results, it might be concluded that lead acetate decreases the volume of pancreatico-biliary secretion and inhibits the amylase activity, by acting directly on pancreatic cells.

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On the Biological Functions of Equine Chorionic Gonadotropin (말의 융모성 성선자극 호르몬의 생화학적 기능)

  • 민관식;윤종택
    • Korean Journal of Animal Reproduction
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    • v.26 no.3
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    • pp.299-308
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    • 2002
  • In horse, a single gene encodes both eCG and eLH $\beta$ subunits. The difference between eCG and eLH lies in the structure of their glycoresidues, which are both sialylated and sulfated in LH and sialylated in CG eCG consists of highly glycosyiated $\alpha$- and $\beta$-subunits and is an unique member of the gonadotropin family because it elicits response characteristics of both FSH and LH in other species than the horse. This dual activity of eCG in heterologous species is of fundamental interest to the study of gonadotropin structure-function relationships and the understanding of the molecular bases of the specific interactions of these hormones with their receptors. Thus, eCG is a dintinct molecule from the view points of its biological function and glycoresidue structures. The oligosaccharide at Asn 56 of the $\alpha$-subunit plays an indispensable role, whereas the carboxyl-terminal extension of the eCG $\beta$-subunit with its associated O-linked oligosaccharides is not improtant for, the in vitro LH-like activity of eCG. In contrast, both N- and O-linked oligosaccharides play important roles for FSH-like activity and increase FSH-like activity by removal of N- and O-linked oligosaccharides. Therefore, the dual LH- and FSH-like activities of eCG can be clearly separated by removal of either the N-linked oligosaccharide on the $\alpha$-subunit or CTP-associated O-linked oligosaccharides from its $\beta$-subunit. The glycoresidues seem to play crucial roles fer biological activities. The tethered-eCG was effciently secreted and showed similar LH-like activity to the dimeric eCG $\alpha$/ $\beta$ and native eCG. FSH-like activity of the tethered-eCG was also shown similarly in comparison with the native and wild type eCG $\alpha$/ $\beta$. Our data for the first time suggest that the tethered-eCG can be expressed efficiently and the produced product by the CHO-Kl cells is fully LH- and FSH-like activities in rat in vitro bioassay system. Our results also suggest that this molecular can imply particular models ot FSH-like activity not LH-like activity in the eCG. Taken together, these data indicate that the constructs of tethered molecule will be useful in the study of mutants that affect subunit association and/or secretion.

Expression of the Circadian Clock Genes in the Mouse Gonad (생쥐 생식소의 발달 단계에 따른 일주기성 유전자 발현에 관한 연구)

  • Chung Mi-Kyung;Choi Yoon-Jeong;Jung Kyenng-Hwa;Kim Eun-Ah;Chung Hyung-Min;Lee Sook-Hwan;Yoon Tae-Ki;Chai Young-Gyu
    • Development and Reproduction
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    • v.8 no.1
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    • pp.57-64
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    • 2004
  • This study was carried out to examine the expression of the circadian clock genes in the mouse ovary and testis at different developmental stages. Expression of Period1(Per 1), Period2(Per2), Period3(Per3), Cryptochrome1(Cry1), Cyptochrome2(Cry2), Clock Small and Prokineticin1 and Prokineticin2 receptor(Prok1r, Prok2r) genes in mouse ovary was explored by semiquantitative reverse transcription Polymerase chain reaction(RT-PCR) according to the developmental stage(post partum day; ppd 1, 7, 10, 21 and 35). Immunohistochemistry using PER1 antibody was also analyzed. The differential expression pattern of clock genes was presented according to stages of the mouse ovarian development (ppd 1, 7, 10, 21 and 35). In the cases of ovaries, at the starting point of follicle growth at ppd 7 and 10, the clock gene expression patterns were changed vastly. According to the developmental stages, the clock genes were highly expressed at ppd 7 and 10 in mouse testis also. Receptors for Prok2, the circadian output molecule of SCN, were also expressed in ovary at ppd 7 and in testis at ppd 1 and 7, respectively. Immnunohistochemical analysis of PER1 showed positive signals in the cytoplasm of oocytes and granulosa cells. The level or PER1 expression was increased in cells at the spermatogonia and the condensing spermatids. The expression pattern of Perl and localization of PER1 were showed similar patterns according to the developmental stages in ovary and testis. Taken together, it could be observed that the expression of clock genes was highly correlated with gonadal development and germ cell differentiation in mice. Therefore, in this study, circadian programming of the genes in the ovary and testis is strongly imposed across a wide range of core reproductive cycles and normal development of gametes. Although the existence of circadian genes is clearly investigated, further studies on the direct evidence is required for the understanding of the relationship between circadian genes and regulation of gonadal differentiation and germ cell development.

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Pressor Action of Intracerebroventricular Nicotine and Muscarine in the Rabbit (가토 측뇌실내 Nicotine 및 Muscarine의 혈압상승작용에 관하여)

  • Lee, Choong-Kyoung
    • The Korean Journal of Pharmacology
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    • v.27 no.1
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    • pp.21-31
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    • 1991
  • When administered intracerebroventricularly (icv), cholinergic nicotinic agents, nicotine and DMPP, as well as cholinergic muscarinic agents, muscarine and bethanechol, produced pressor responses in urethane-anesthetized vagotomized rabbits. The response patterns to nicotine and to DMPP were similar, while the bethanechol response resembled the muscarine pattern. The pressor response to nicotine and DMPP was markedly inhibited by icv mecamylamine but not by icv pirenzepine, whereas the response to muscarine and bethanechol was inhibited by icv pirenzepine but not by icv mecamylamine, suggesting that both nicotinic and muscarinic receptors in the brain are involved in the action. Intravenous pretreatments of animals with regitine, reserpine, enalapril, saralasin, both regitine and enalapril, both regitine and saralasin, SK&F-100273 did not prevent the pressor response to nicotine and muscarine. Iv pretreatments with both regitine and SK&F-100273 inhibited the nicotine response without affecting the muscarine response, whereas pretreatments with three agents, regitine, enalapril and SK&F-100273, inhibited the muscarine response. The nicotine-induced elevated blood pressure as well as the muscarine-induced were lowered by regitine but not by enalapril or by SK&F-100273. Enalapril was without effect on the nicotine hypertension in rabbits treated with regitine or both regitine and SK&F-100273, whereas SK&F-100273 lowered the nicotine hypertension in regitine-treated animals. Enalapril did not enhance the lowering effect of SK&F-100273 in regitine-treated ones, nor did it cause a fall of the muscarine hypertension induced in regitine-treated rabbits, but it did lower the blood pressure in animals treated with both regitine and SK&F-100273. Likewise, SK&F-100273 did not cause a fall of the muscarine hypertension induced in regitine-treated rabbits, but it did lower the blood pressure in animals treated with both regitine and enalapril. These data suggest that the nicotine-induced hypertensive state is related to at least two systems in the periphery-sympathetic and vasopressin, whereas in the muscarine-induced hypertensive state three systems in the periphery are involved, i.e., the sympathetic, vasopressin and angiotensin system. The hypotensive effect of regitine on basal arterial blood pressure levels of rabbits was not influenced by pretreatment with either of enalapril or SK&F-100273, but significantly potentiated by treating with both enalapril and SK&F-100273, suggesting participation of the sympathetic and the renin-angiotensin system as well as the vasopressin system in maintenance of arterial blood pressure.

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