• Biomolecules & Therapeutics
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• v.5 no.3
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• pp.239-245
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• 1997

Trimetoquinol (TMQ) and its analogs are known to have thromboxane $A_2$ antagonistic action. We also reported that GS389, chemically similar to TMQ, has competitive antagonistic action in rat aorta and human platelets. In the present study, we investigated the pharmacological characteristics of GS283 and GS 386, analogs of GS389, using vascular smooth muscle, human platelets and rat brain homogenates. In isolated pig coronary artery (PCA), both of GS283 and GS386 relaxed U46619-contracted rings in concentration dependent manner. Pretreatment with several concentrations of GS283 and GS386 shifted the dose-response curves to the right, and reduced of maximum contration dose-dependently. Furthermore, GS283 and GS386 strongly inhibited $Ca^{2+}$ -induced contraction in the PCA. In human platelets, U46619- and A23187-induced platelet aggregation was inhibited by GS283 and GS386, concentration-dependently. Anti-platelet aggregation was related to the compound\`s ability to inhibit ATP release at each stimulation. In rat brain homogenates, receptor-binding assay resulted that both GS283 and GS386 have a relative affinity to $\alpha$-adrenergic receptor. Taken together. we concluded that the mechamism of action of GS283 and GS86 is not related with in TXA$_2$ receptor but concerned with calcium antagonistic action and a-blocking action.n.

• Journal of Acupuncture Research
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• v.17 no.4
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• pp.149-159
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• 2000

Bee-venom Acupucture has good effect on pain control but We may be anxious about the problem of side-effect. Bee-venom components are composed of phospholipase $A_2$, hyaluronidase, melitin, apamin, MCD peptide, citrate and so on. Especially Apamin, MCD peptide and histamine cause severe reacting that is named Anaphylaxis. Anaphylaxis is a clinical syndrome characterized by the acute system reaction of multiple organ systems to an IgE-mediated immunologic mediator release in previously sensitized individuals. Respiratory and dermatologic manifestations are the most commonly expressed clinical features of anaphylaxis, and a majority of anaphylactic reactions initially appear to be localized to these two systems. Anaphylatic reaction of bee-venom are expressed clinically ulticaria, itching sensation, erythema, dizziness, nausea, hypotension and so on. Especially ulticaria and erythema are end points of increased vascular permeability and vasodilatation at the other extreme of the clinical spectrum, Gastrointestinal mucosal edema and smooth muscle contraction can result in cramping abdominal pain, nausea, and vomiting. Therefore, we have observed anaphylatic reaction of bee-venom in 11 patients, who visited WonKwang University Kunpo Oriental Medical Center, treated bee venom. The results were summarized as follows : 1. The patient distribution ratio, in regard to sex, was shown to be 1 : 2.67 for male to females. In regard to age, it was shown that people in their 30's was the most predominant case, followed by people in their 20's, 30's, 50's and 60's, respectively. 2. When Anaphylaxis was occured, it was observed to abnormality of CBC, LFT, IgE, IgG. 3. In regard to patient condition, it was observed that fatigue was most frequent. 4. In regard to the number of times and quantity of bee venom inj., it was observed that anaphylaxis is most frequent at 7-10 times(1.6-2.0cc) 5. In regard to duration of reaction, it was observed that people in their l0min' was most frequent. In disappearing duration of anaphylaxic reaction, The results showed under 60min lcases(9%), 60-120min 7cases(64%) and 180-240min 3cases(27%). 6. In symptoms of anaphylaxis, The results showed hypotension 8cases(19%), itching sensation 7cases(16%), nausea 4cases(9%), erythema 4cases(9%) and dizziness 4cases(9%). In mentality, The results showed drowsy 8case(73%) and alert 3cases(27%). 7. Generally, patients were treated with Avil, Dexa IM and PDS, peniramine, cimetidine, Q-zyme per os after H/S, N/S inj. $O_2$ was supplied according to patient's symptom. In 1 severe case, Dopamine was iv injected.

• The Korean Journal of Pharmacology
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• v.31 no.3
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• pp.291-297
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• 1995

The objectives of this study is to compare the inhibitory mechanism of sodium nitroprusside and forskolin on the phorbol ester, activator of protein kinase C (PKC), -induced contractions in rat aorta. $0.1\;{\mu}M$ phorbol dibutyrate (PDBu) induced sustained contractions and increased phosphorylations of myosin light chain (MLC) time-dependently. At 30 min, the contractions and phosphorylations of MLC by PDBu were augmented maximally and remained constant. Moreover, $^{45}Ca^{2+}$ uptake was increased 30 min after PDBu stimulation from resting values. Sodium nitroprusside which activates guanylyl cyclase followed by increasing cGMP, inhibited the PDBu-induced contractions concentration-dependently. On the other hand, forskolin which activates adenylyl cyclase followed by increasing cAMP, also inhibited the PDBu-induced contractions concentration-dependently. However, sodium nitroprusside was more potent to inhibition of the PDBu-induced contractions than forskolin. Sodium nitroprusside inhibited $^{45}Ca^{2+}$ uptake by PDBu stimulation. Forskolin also inhibited $^{45}Ca^{2+}$ uptake by PDBu stimulation. Sodium nitroprusside and forskolin inhibited the phosphorylations of MLC by PDBu, respectively. However, sodium nitroprusside was more potent to inhibition of phosphorylations of MLC by PDBu than forskolin. From these results, Sodium nitroprusside via cGMP or forskilin via cAMP may reduce myoplasmic $Ca^{2+}$ followed by suppression of phosphorylations of MLC of PKC-mediated contractions, which results in vasodilation. However, cGMP may play a role more importantly than cAMP on the regulation of protein kinase C-mediated contraction in vascular smooth muscle.

• Journal of Chest Surgery
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• v.36 no.12
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• pp.887-893
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• 2003

External stimuli increases intracellular (IC) $Ca^{2+}$, which increases extracellular (EC) $K^{+}$. To verify $K^{+}$ effects on the vascular contraction, we performed an experiment using mouse aortic endothelial cell. Meterial and Method: We examined the mouse aortic contractility changes as we measured the IC $Ca^{2+}$ change and ionic current by using the voltage clamp technique under different conditions such as: increasing EC $K^{+}$, removing endothelial cell, giving L-NAME (N-nitro-L-arginine methyl ester) which suppress nitric oxide formation, Ouabain which control N $a^{+}$ - $K^{+}$ pump and N $i^{2+}$ which repress N $a^{+}$-C $a^{2+}$ exchanger Result: When we increased EC $K^{+}$ from 6 to 12 mM, there was no change in aortic contractility. Aorta contracted with more than 12 mM of EC $K^{+}$. Ace-tylcholine (ACh) induced relaxation was inhibited with EC $K^{+}$ from 6 to 12 mM, but was not found after de-endothelialization or L-NAME treatment. ATP or ACh increased IC $Ca^{2+}$ in cultured endothelium. After maximal increase of IC $Ca^{2+}$, increasing EC $K^{+}$ from 6 to 12 mM made IC $Ca^{2+}$ decrease and re-decreasing EC $K^{+}$ to 6 mM made IC $Ca^{2+}$ increase. Ouabain and N $i^{2+}$ masked the inhibitory effect of endothelium dependent relaxation by increased EC $K^{+}$. Conclusion: These data indicate that increase in EC $K^{+}$ relaxes vascular smooth muscle and reduces $Ca^{2+}$ in the endothelial cells which inhibit endothelium dependent relaxation. This inhibitory mechanism may be due to the activation of N $a^{+}$- $K^{+}$ pump and N $a^{+}$-C $a^{2+}$ exchanger. $a^{+}$-C $a^{2+}$ exchanger.r.