• IMMUNE NETWORK
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• v.4 no.2
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• pp.108-115
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• 2004

Background: Production of nitric oxide (NO) by inducible NO synthase (iNOS) has been implicated in the pathology of autoimmune disease. It is unknown whether iNOS expression is increased within testes and whether iNOS and NO have essential roles in the pathogenesis of EAO. Methods: EAO was induced in guinea pig testes at 17 days after secondary immunization by administration of crude extract (CE) and purified glycoprotein 1 (GP1) from normal guinea pig testes. iNOS gene expression was assessed by RT-PCR and Northern blot analysis in testes. Localization of iNOS and Mac-1 and the indicator of NO-mediated tissue injury, nitrotyrosine, were detected in the testicular lesion by immunohistochemistry. Results: In control testes, inflammation and iNOS gene expression were not detected, whereas, in CE- and GP1-injected testes, inflammation and marked iNOS gene expression were evident at day 17 after secondary immunization. Immunohistochemistry of Mac-1 showed the colocalization with iNOS protein and nitrotyrosyl proteins in intertubules, suggesting that NO produced by infiltrated macrophages may be involved in inflammatory lesions of intertubules. Intraperitoneal administration of aminoguanidine significantly prevented EAO with reduction of inflammation, iNOS expression and nitrotyrosine formation. Conclusion: These results suggest that NO production by macrophages may be important in the pathogenesis of CE- and GP1-induced EAO. Furthermore, this study demonstrated the therapeutic potential of iNOS inhibitor in the treatment of inflammatory and autoimmune mediated-diseases.

• Proceedings of the Ginseng society Conference
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• 1993.09a
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• pp.84-93
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• 1993

It has been reported that ginseng is effective in the central nervous system, immune system, and the strong inflammatory responses. However, there has been no research report yet about the effect of ginseng on allergic hypersensitivity reactivity. To confirm the ginseng effects on the release of mediators(histamine. leukotrienes etc.) which cause the hypersensitivity reactivity and inflammatory response, we used actively sensitized guinea pig airway tissues by utilizing the superfusion technique. In this procedure. the contractile response and mediators released after antigen stimulation of sensitized tissues, and IgG and IgE antibody products were measured in sera of immunized animals. Then the results of the controll group were compared to those of ginseng pretreatment groups. In the total saponin(TS) and panaxatriol(PT) pretreatment, histamine release decreased by $20\%$ in the tracheal tissues after active sensitization by ovalbumin(OVA, 10mg/kg), but in the lung parenchyma, histamine release decreased by $40\%.$ Panaxadiol(PD) significantly decreased histamine release by $40\%$ in the both tissues after active sensitization. TS, PT and PD of ginseng poorly blocked leukotrienes (LTs) and prostagrandin $D_2(PGD_2)$ release(less than $10\%$). Ginseng TS and PT had no effect on the serum IgG antibody production by ovalbumin, whereas PD significantly increased serum IgG antibody contents(approximately by 2 times). However, $IgG_1$ antibody products in the serum of guinea pig actively sensitized with ovalbumin after PD pretreatment were decreased, compared to that with ovalbumin alone. IgE antibody production by passive cutaneous anaphylaxis(PCA) titer in the TS pretreatment increased 3 times more than in the absence of TS(PCA titer by PT was not detected). These studies show that some ginseng saponins can in part act to inhibit mediator release in antigen - induced airway smooth muscle by inducing the IgG antibody production which has been changed in the specificity.

• The Korean Journal of Physiology and Pharmacology
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• v.4 no.6
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• pp.479-486
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• 2000

The aim of this study was to clarify the mechanism of the inhibitory action of carbon monoxide (CO) on contraction, by measuring cytosolic $Ca^{2+}$ level $([Ca^{2+}]_i)$ and ionic currents in guinea-pig ileum. CO (10%) inhibited 40 mM KCl-induced contraction and this effect was blocked by ODQ $(1\;{\mu}M),$ a soluble guanylyl cyclase (sGC) inhibitor. CO inhibited the 40 mM KCl-induced contraction without changing $[Ca^{2+}]_i.$ Cumulative addition of KCl induced a graded increase in $[Ca^{2+}]_i$ and muscle tension. In the presence of CO, cumulative addition of KCl induced smaller contraction than in the absence of CO. On the other hand, the increase in $[Ca^{2+}]_i$ induced by cumulative addition of KCl was only slightly decreased in the presence of CO, and the $[Ca^{2+}]_i-tension$ relationship shifted downwards. Using the patch clamp technique with a holding potential of -60 mV, we found that CO had little effect on the peak Ba currents $(I_{Ba})$ when voltage was stepped from -60 mV to 0 mV. In addition, CO showed no effect on the depolarization-activated outward $K^+$ currents in the all potential ranges. We conclude that CO inhibits smooth muscle contraction mainly by decreasing the $Ca^{2+}$ sensitivity of contractile elements via a cGMP-dependent pathway, not by involving L-type $Ca^{2+}$ and outward-potassium currents in guinea-pig ileum.

• The Korean Journal of Physiology and Pharmacology
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• v.12 no.6
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• pp.323-330
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• 2008

The properties of voltage dependent $Ca^{2+}$ current (VDCC) were investigated in interstitial cells of Cajal (ICC) distributed in the myenteric layer (ICC-MY) of guinea-pig antrum. In tissue, ICC-MY showed c-Kit positive reactions and produced driving potentials with the amplitude and frequency of about 62 mV and 2 times $min^{-1}$ respectively, in the presence of $1{\mu}M$ nifedipine. Single ICC-MY isolated by enzyme treatment also showed c-Kit immunohistochemical reactivity. These cells were also identified by generation of spontaneous inward current under $K^+$ -rich pipette solution. The voltage clamp experiments revealed the amplitude of - 329 pA inward current at irregular frequency. With $Cs^+$-rich pipette solution at $V_h=-80\;mV$, ICC-MY produced voltage-dependent inward currents (VDIC), and nifedipine ($1{\mu}M$) blocked VDIC. Therefore, we successfully isolated c-Kit positive single ICC from guinea-pig stomach, and found that ICC-MY potently produced dihydropiridine sensitive L-type voltage-dependent $Ca^{2+}$ currents ($VDCC_L$).

• Korean Journal of Veterinary Research
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• v.40 no.4
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• pp.691-699
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• 2000

We investigated the effects of nitric oxide (NO) donors, S-nitroso-L-cysteine (Cys-NO) and 3-morpholinosydnonimine hydrochloride (SIN-1), on the contractile and electrical activity of the circular muscle of guinea pig gastric antrum by using intracellular microelectrode technique. The gastric antral circular muscle showed spontaneous phasic contraction and slow wave of membrane potential. Cys-NO ($0.001{\sim}10{\mu}M$) and SIN-1 ($0.001{\sim}100{\mu}M$) reduced not only the tonic and phasic contraction but also the amplitude of slow wave in a concentration dependent manner. NO donors were more potent to inhibit phasic contraction than to do slow wave. These inhibitory effects of NO donors were mimicked by the membrane permeable guanosine-3',5'-cyclic monophosphate (cGMP) analogue, 8-bromo-cyclic GMP (8-br-cGMP, $10{\sim}300{\mu}M$). The inhibitory effects of SIN-1 and Cys-NO were antagonized by the guanylate cyclase inhibitor, 1H[ [1,2,4]oxadiazolo[4,3,-a]quinoxalin-1-one (ODQ, $10{\mu}M$). These results suggest that the inhibitory effects of NO donors on the mechanical and electrical activity is mainly mediated by cGMP pathway.

• YAKHAK HOEJI
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• v.33 no.3
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• pp.167-174
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• 1989

KR-1008 and KR-30006 are 1,4-dihydropyridine derivatives, new vasodilatory calcium antagonists from KRICT. Calcium antagonistic properties of the compounds were studied in the isolated heart (Langendorff preparation), pulmonary artery (vasodilation), and in the papillary muscle (negative inotropic effect) of the guinea pig. Antihypertensive effect were also investigated after i.v. or oral administration in the SHR (spontaneously hypertensive rat). They produced a sigificant inhibition of Ca-induced contraction in the guinea pig pulmonary artery at the concentrations of above $10^{-8}M$. The negative inotropic effect of the electrically stimulated papillary muscle appeared from the concentration of $10^{-6}M$, which is about hundred times higer than the concentration of vasodilation effect. Left ventricular pressure also decreased from the concentration of $3\;{\times}\;10^{-6}M$ in KR-1008 and KR-3006 in the Langendorff heart preparations. Coronary flow rate increased from $10^{-6}M$ in KR-1008 and nicardipine and appeared no change in KR-30006. The antihypertensive effect of KR-1008 (EC 20: $2.9\;{\mu}g/kg$) was potent more than nicardipine (EC 20: $3.4\;{\mu}g/kg$) and than Kr-30006 (EC 20: $6.8\;{\mu}g/kg$) was, after i.v. bolus injection in the anesthetized SHR. The antihypertensive effect in the conscious SHR appeared 30 minutes after oral administration of 10 mg/kg and persisted 4 hrs in KR-1008 and 12 hrs in KR-30006. Heart rate tended to increase for 0.5-1 hr after oral administration of the test compounds.

• Korean Journal of Veterinary Research
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• v.32 no.1
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• pp.41-49
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• 1992

Higenamine is an Aconiti tuber derived compound whose chemical structure is 1-(4'-hydroxybenzyl)-6, 7-dihydroxy-1, 2, 3, 4-tetrahydroisoquinoline containing catechol ring and tetrahydroisoquinoline nucleus in its own structure, both of which are well known to have agonistic effects on adrenergic receptors. Using guinea-pig atria(rich in ${\beta}_1$-receptor) and treachea(rich in ${\beta}_2$-receptor), we studied pharmacological actions of higenamine on these organs with special interest of its relevancy of ${\beta}$-receptor selectivity. In order to further clarify its pharmacological characteristics, the influncences of pretreatment of reserpine or cocaine were also investigated. The results were summarized as follows : 1. Higenamine had remarkable chronotropic, inotropic and bronchodilator effects in guinea-pig spontaneously beating right atria, left atria and trachea, in dose-dependent manners. 2. All of above actions were blocked competitively by propranolol, which shows nonselectivity of higenamine on ${\beta}$-receptor. $pA_2$ values of propranolol against higenamine were 7.93, 7.76 and 8.46 in guinea-pig right atria, left atria and treachea, respectively. 3. Reserpine pretreatment(5mg/kg, ip, 24h) did not show my decrease in pharmacological actions of higenamine, which suggests higenamine has direct action on ${\beta}$-receptor not via catecholamine release. 4. Cocaine pretreatment$(1{\mu}M)$ had no influence on pharmacological actions of higenamine in contrast with nor epinephrine, which suggests there is no neuronal uptake mechanism of higenamine in the studied organ preparations.

• Korean Journal of Microbiology
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• v.23 no.4
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• pp.291-296
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• 1985

Leptospira isolated from patients and natural paddy water were further studied to confirm their serologic specificity with the bacteria in infected animal tissue and autopsied tissue of patients died with leptospirosis. And pathologic patterns of the inoculated antimal and the virulence of the bacteria in the animals were also studied. The findings are summarized as follows; $LD_{50}$ dose of the bacteria in guinea-pig were $1-2{\times}10^9$ cells and mice were found to be susceptible to them even though the degree of susceptibilities were much inferior to guinea pig. The bacteria were recovered from various organs; demonstrated massive hemorrages due to diapedesis and monocyte infiltration were observed, in some cases, intramedullary hemorrages of the infected kidnies and hematuria were recognized. All of the hyperimmune sera were strongly reacted with the tissues from autopsied human case who died of EPHF(Epidemic Pulmonary Hemorrhagic Fever) in immunofluorescent antibody tests.

• Korean Journal of Veterinary Research
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• v.36 no.2
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• pp.327-335
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• 1996

Recently in spite of the interest on the regulation of intracellular $Mg^{2+}$ by neurotransmitters or drugs, the magnesium ion($Mg^{2+}$) regulation by ${\alpha}_1$-adrenoceptor stimulation has not been studied in the heart yet. To elucidate the regulation of ${\alpha}_1$-adrenoceptor stimulation-induced $Mg^{2+}$ release and the effects of ${\alpha}_1$-adrenoceptor stimulation on pathophysiological conditions, in this study we have evaluated the effects of phenylephrine, PMA, $H_7$. staurosporine, verapamil and lidocaine on $Mg^{2+}$ release in perfused guinea pig heart. During preperfusion exogenous $Mg^{2+}$ was added to the medium to give 1.2mM 15min before starting to addition of drugs, and then the infusion of exogenous $Mg^{2+}$ was stopped. $Mg^{2+}$ in the perfusate leaving the heart was measured by atomic absorption spectrophotometry. $Mg^{2+}$ free solution produced an increase in heart rate and phenylephrine elicited $Mg^{2+}$ release from the heart. $Mg^{2+}$ release by phenylephrine was abolished by combined treatment with prazosin. By contrast, cardiac $Mg^{2+}$ uptake induced by a protein kinase C(PKC) activator, PMA was abolished by a selective PKC inhibitor, staurosporine. And the phenylephrine-induced $Mg^{2+}$ release was not affected by the PKC inhibitor, $H_7$. When verapamil or lidocaine was added to perfusing solution, $Mg^{2+}$ release was potentiated by phenylephrine from perfused guinea pig heart. These results suggest that ${\alpha}_1$-adrenoceptor stimulation caused $Mg^{2+}$ release and that PKC is not involved in ${\alpha}_1$-adrenoceptor mediated $Mg^{2+}$ release from perfused guinea pig heart. Under pathophysiological conditions, the $Mg^{2+}$ alteration by ${\alpha}_1$-adrenoceptor stimulation is considerable.

• The Korean Journal of Zoology
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• v.25 no.1
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• pp.9-28
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• 1982

Cyclical changes in the fine structures of the surface epithelial, stroma and glandular cells of guinea pig endometrium during the estrous cycle were studied by transmission and scanning electron microscopy. Cytochemical studies were made in order to investigate the ultrastructural localization of the acid phosphatase, alkaline phosphatase and ATPase in these cells. The results obtained are as follows: 1. The endometrial surface epithelium was pseudostratified columnar during estrus and meterstrus, and simple columnar during proestrus and diestrus. The characteristic features observed in these cells include increased nucleocytoplasmic ratio at proestrus, elongated shapes of both the nucleus and the entire cell, increased volume of the cytoplasm and cytoplasmic bulding into the lumen during estrus, and smaller surface epithelial cells during metestrus. 2. In the cytoplasm of surface epithelial cells, the numbers of mitochondria and free ribosomes were increased, and rough endoplasmic reticulum and Golgi complex appeared during estrus, and the degenerated cells, lipid droplets, multilamellated bodies and lysosomes appeared during diestrus. 3. During estrus, scanning electron microscopic observations of endometrial surface showed a regular arrangement with polygonal outlines of epithelial cells, distinct intercellular border, and bulged surface into the lumen, whereas flat surface and indistinct cell border were characteristic during meterstrus and diestrus. 4. Microvilli which aligned on the surface were longer and most abundant during estrus while short and aparse during other phases. 5. Cytochemical studies indicated that during metestrus acid phosphatase activities were localized in the microvilli and vacuoles, and alkaline phosphatase activities were significant around luminal surface and lateral cell membrane in the surface epithelial cells. ATPase activities were present on the microvilli and cell membrane during proestrus and estrus.