• 한국임상수의학회지
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• 제7권2호
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• pp.501-509
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• 1990

This study was designed to examine effects of $\alpha$$_2$-Adrenergic Antagonists on blood chemical values in xylazine-sedated dogs. Twenty-four crossbred dogs of both sexes were intramusculary injected with a standard dosage of xylazine(2.2mg/kg of body weight). Righting reflex was uniformly lost and considered to be the point of maximum sedation. When the dogs were maximally sedated, tested groups were in-travenously injected with yohimbine 0.125mg/kg, 4-aminopyridine(4-AP) 0.3mg/kg, and a combination of yohimbine with 4-AP. Control group was intravenously 1 $m\ell$ of physiological saline solution. Total protein(T.P), albumin, glucose, aspartate aminotransferase(AST), alanine aminotrnasferase(ALT), blood urea nitrogen(BUN) were analyzed in the conditions of 0-, 30-, 60- and 120-minute after the administration of drugs. The results obtained in the study were as follows. 1. Changes of T.P, albumin, AST, ALT and BUN values in the control group were not significant during or after xylazine administration for at least 120minutes. 2. No changes of T.P, albumin, AST, ALT and BUN values in the tested groups were observed during or after $\alpha$$_2$-Adrenergic Antagonists treatment. 3. Serum glucose values of control group were getting remarkably increased after xylazine injection. 4. The xylasine-induced hyperglycemia was reversed in the dogs administrated with $\alpha$$_2$-Adrenergic Antagonists. Therefore, the results of the study show that the combined treatment with antagonists may be useful for accidental overdoses of xylazine and rapid reversal of animals sedated with xylazine.

• 대한약리학회지
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• 제27권2호
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• pp.99-108
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• 1991

Racemic ketamine을 사용하여 개구리의 좌골신경 및 toe muscle에 대한 작용을 관찰하였다. 실험방법으로는 214 mM sucrose을 사용하여 서로 다른 두 종류의 투여 방법으로 세포막의 활동 전압에 대한 영향을 electric recording으로 관찰하였다. 즉, intracellular 투여는 single sucrose gap technique으로, extracellar 투여는 double sucrose gap technique을 사용하였으며 그 실험 결과는 아래와 같았다. 1. Racemic ketamine은 개구리의 좌골신경 및 toe muscle의 활동전압을 intracellular 및 extracellular 투여시 모두 의의 있게 억제하였다. 2. 개구의 toe muscle에서 $K^+$-수축을 억제하였다. 3. naloxone은 ketamine의 억제작용을 완전히 차단하지는 못하였다.

• The Korean Journal of Physiology and Pharmacology
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• 제12권4호
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• pp.131-135
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• 2008

The profile of membrane currents was investigated in differentiated neuronal cells derived from human neural stem cells (hNSCs) that were obtained from aborted fetal cortex. Whole-cell voltage clamp recording revealed at least 4 different currents: a tetrodotoxin (TTX)-sensitive $Na^+$ current, a hyperpolarization-activated inward current, and A-type and delayed rectifier-type $K^+$ outward currents. Both types of $K^+$ outward currents were blocked by either 5 mM tetraethylammonium (TEA) or 5 mM 4-aminopyridine (4-AP). The hyperpolarization-activated current resembled the classical $K^+$ inward current in that it exhibited a voltage-dependent block in the presence of external $Ba^{2+}$ (30 ${\mu}$M) or $Cs^+$ (3${\mu}$M). However, the reversal potentials did not match well with the predicted $K^+$ equilibrium potentials, suggesting that it was not a classical $K^+$ inward rectifier current. The other $Na^+$ inward current resembled the classical $Na^+$ current observed in pharmacological studies. The expression of these channels may contribute to generation and repolarization of action potential and might be regarded as functional markers for hNSCs-derived neurons.

• 동의생리병리학회지
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• 제24권4호
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• pp.592-597
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• 2010

Cinnamomi Ramulus is one of the medicinal plants that have been used to improve various diseases caused by insufficient blood circulation. This study was performed for the investigation of vasodilation efficacy ethanol extract of Cinnamomi Ramulus (CR). CR exhibited vascular relaxation against phenylephrine (PE, $10^{-6}M$)-, KCl- and NaF-induced contraction in rat thoracic aorta. In addition, its relaxation was endothelium-independent. Treatment of potassium channel blockers such as gilbenclamide (Gli, $10^{-5}M$), tetraethylammonium (TEA, 1 mM) and 4-aminopyridine (4-AP, 0.2 mM) did not effect on the relaxation of CR. The relaxant effects were also not inhibited by pre-treatment of rat aorta with L-NAME ($10^{-4}M$), methylene blue ($10^{-5}M$), indomethacin ($10^{-5}M$), and atropine ($10^{-6}M$). However, nifedipine ($10^{-5}M$), L-type $Ca^{2+}$ channel blocker, in part attenuated the relaxation of CR ($0.2\;mg/m{\ell}$), but SK&F96365 ($3{\times}10^{-5}M$), receptor activated $Ca^{2+}$ channel blocker and 2-APB ($10^{-4}M$), store operated $Ca^{2+}$ channel blocker did not affact dilation of CR. These findings suggest that the endothelium-independent relaxation effect of CR is partly related with inhibition of $Ca^{2+}$ influx via voltage dependent $Ca^{2+}$ channel.

• 약학회지
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• 제41권4호
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• pp.399-406
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• 1997

The effects of different $K^+$ channel blockers were investigated on the non-adrenergic non-cholinergic (NANC) relaxations in the circular muscle of the rabbit proximal stomach. Non-selective blockers of $K^+$ channels, 4-aminopyridine (4-AP, 3~30${\mu}M$) and tetraethylammonium (TEA, 100~1000${\mu}M$) significantly enhanced the NANC relaxations in a concentration-dependent manner. The enhancement was more prominent for the NANC relaxations induced by the electric field stimulation (EFS) with lower frequencies. Blockers of large conductance $Ca^{2+}$-activated $K^+$ channels, charybdotoxin and iberiotoxin, a blocker of small conduntance $Ca^{2+}$-activated $K^+$ channels, apamin and a blocker of ATP-sensitive $K^+$ channels, glibenclamide had no effect on the NANC relaxations, respectively. Exogeneous administration of nitric oxide (NO, 1~30${\mu}M$) caused concentration-dependent relaxations which showed a similarity to those obtained with EFS. None of the $K^+$ channel blockers had an effect on the concentration-dependent relaxation in response to NO. These results suggest that prejunctional $K^+$ channels regulate the release of NO from the NANC nerve in the rabbit proximal stomach as the inhibition of prejunctional $K^+$ channels increases the NANC relaxation induced by the EFS.

• The Korean Journal of Physiology
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• 제23권2호
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• pp.301-312
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• 1989

It well known that the magnitude of contraction and the shape of action potential depend upon the stimulation frequency and the duration of resting period (positive and negative staircase). Although the underlying mechanism of the staircase phenomenon is not fully understood, it has been suggested that staircase could be related to the intracllular $Ca^{2+}$ concentration. In order to elucidate the role of intracellular $Ca^{2+}$ on the contraction and action potential staircases, we examined the effects of 1 mM 4-aminopyridine (4-AP), 0.5 uM verapamil, 1 uM ryanodine, or reduction of extracellular Na concentration to 30% $(substituted\;by\;equimolar\;Li^+)$ in small atrial strips of the rabbit $(3{\times}10\;mm)$. The results obitained were as follows; 1) When the stimulation frequency was increased from 0.1 Hz to 2 Hz, positive staircase of the contraction and elevation of plateau level in action potential were found in control and the conditions of Na reduction and treatments of 4-AP, verapamil and ryanodine. 2) When stimulation frequency returned to 0.1 Hz from 1 min rest just after 2 Hz stimulation fer 1 min, the magnitudes of initial few contractions were larger than that of steady state contraction (post-rest potentiation) except, ryanodine or Na-reduction groups. 3) Negative staircase of contraction was developed in control and 4-AP group at post-rest 0.1 Hz stimulation and the plateau level of the action potential was decreased at the same time. But the reduction of contraction or the plateau level was much smaller in 4-AP group and than in control. From the above results it can be concluded that contraction and action potential staircase is dependent upon transmembrane $Ca^{2+}-current\;and\;Ca^{2+}$release from the SR.

• The Korean Journal of Physiology and Pharmacology
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• 제1권6호
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• pp.783-796
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• 1997

The relaxation induced by stimulation of the inhibitory non-adrenergic, non-cholinergic (iNANC) nerve is mediated by the release of iNANC neurotransmitters such as nitric oxide (NO), vasoactive intestinal peptide (VIP) and adenosine triphosphate (ATP). The mechanisms of NO, VIP or ATP-induced relaxation have been partly determined in previous studies, but the detailed mechanism remains unknown. We tried to identify the nature of iNANC neurotransmitters in the smooth muscle of guinea pig ileum and to determine the mechanism of the inhibitory effect of nitric oxide. We measured the effect of NO-donors VIP and ATP on the intracellular $Ca^{2+}$ concentration$([Ca^{2+}]_i)$, by means of a fluorescence dye(fura 2) and tension simultaneously in the isolated guinea pig ileal smooth muscle. Following are the results obtained. 1. Sodium nitroprusside $(SNP:10^{-5}\;M)$ or S -nitro-N-acetyl-penicillamine $(SNP:10^{-5}\;M)$ decreased resting $[Ca^{2+}]_i$ I and tension of muscle. SNP or SNAP also inhibited rhythmic oscillation of $[Ca^{2+}]_i$ and tension. In 40mM $K^+$ solution or carbachol ($(CCh:10^{-6}\;M)$-induced precontracted muscle, SNP decreased muscle tension. VIP did not change $[Ca^{2+}]_i$ and tension in the resting or precontracted muscle, but ATP increased resting $[Ca^{2+}]_i$ and tension in the resting muscle. 2. 1H-[1,2,4]oxadiazol(4,3-a)quinoxalin-1-one $(ODQ:1\;{\mu}M)$, a specific inhibitor of soluble guanylate cyclase, limited the inhibitory effect of SNP 3. Glibenclamide $(10\;{\mu}M)$, a blocker of $K_{ATP}$ channel, and 4-aminopyridine (4-AP:5 mM), a blocker of delayed rectifier K channel, apamin $(0.1\;{\mu}M)$, a blocker of small conductance $K_{Ca}$ channel had no effect on the inhibitory effect of SNP. Iberiotoxin $(0.1\;{\mu}M)$, a blocker of large conductance $K_{Ca}$ channel, significantly increased the resting $[Ca^{2+}]_i$, and tension, and limited the inhibitory effect of SNP. 4. Nifedipine $(1\;{\mu}M)$ or elimination of external $Ca^{2+}$ decreased not only resting $[Ca^{2+}]_i$ and tension but also oscillation of $[Ca^{2+}]_i$ and tension. Ryanodine $(5\;{\mu}M)$ and cyclopiazonic acid $(10\;{\mu}M)$ decreased oscillation of $[Ca^{2+}]_i$ and tension. 5. SNP decreased $Ca^{2+}$ sensitivity of contractile protein. In conclusion, these results suggest that 1) NO is an inhibitory neurotransmitter in the guinea pig ileum, 2) the inhibitory effect of SNP on the $[Ca^{2+}]_i$ and tension of the muscle is due to a decrease in $[Ca^{2+}]_i$ by activation of the large conductance $K_{Ca}$ channel and a decrease in the sensitivity of contractile elements to $Ca^{2+}$ through activation of G-kinase.

• 동의생리병리학회지
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• 제29권6호
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• pp.492-497
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• 2015

In the present study, vasorelaxant effect of the extract of seeds of Oenothera odorata (SOO) and its possible mechanism responsible for this effect were examined in vascular tissues isolated from rats. Changes in vascular tension, 3',5'-cyclic monophosphate (cGMP) levels were measured in thoracic aorta rings from rats. Methanol extract of seeds of Oenothera odorata relaxed endothelium-intact thoracic aorta in a dose-dependent manner. A dose-dependent vascular relaxation was also revealed by treatment of ethylacetate, n-butanol, and H₂O (aqua extract of seeds of Oenothera odorata , ASOO) extracts partitioned from methanol, but not by hexane extract. However, the vascular relaxation induced by ASOO were abolished by removal of endothelium of aortic tissues. Pretreatment of the endothelium-intact vascular tissues with N^G-nitro-L-arginine methyl ester (L-NAME) or ¹H-[1,2,4]-oxadiazole-[4,3-α]-quinoxalin-1- one (ODQ) significantly inhibited vascular relaxation induced by ASOO. Moreover, incubation of endothelium-intact aortic rings with ASOO increased the production of cGMP. However, ASOO-induced increases in cGMP production were blocked by pretreatment with L-NAME or ODQ. The vasorelaxant effect of ASOO was attenuated by tetraethylammonium (TEA), 4-aminopyridine, and glibenclamide attenuated. On the other hand, the ASOO-induced vasorelaxation was not blocked by verapamil, and diltiazem. Taken together, the present study demonstrates that ASOO dilate vascular smooth muscle via endothelium-dependent NO-cGMP signaling pathway, which may be closely related with the function of K⁺ channels.

• The Korean Journal of Pain
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• 제27권3호
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• pp.229-238
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• 2014

Background: A toxic dose of bupivacaine produces vasodilation in isolated aortas. The goal of this in vitro study was to investigate the cellular mechanism associated with bupivacaine-induced vasodilation in isolated endothelium-denuded rat aortas precontracted with phenylephrine. Methods: Isolated endothelium-denuded rat aortas were suspended for isometric tension recordings. The effects of nifedipine, verapamil, iberiotoxin, 4-aminopyridine, barium chloride, and glibenclamide on bupivacaine concentration-response curves were assessed in endothelium-denuded aortas precontracted with phenylephrine. The effect of phenylephrine and KCl used for precontraction on bupivacaine-induced concentration-response curves was assessed. The effects of verapamil on phenylephrine concentration-response curves were assessed. The effects of bupivacaine on the intracellular calcium concentration ($[Ca^{2+}]_i$) and tension in aortas precontracted with phenylephrine were measured simultaneously with the acetoxymethyl ester of a fura-2-loaded aortic strip. Results: Pretreatment with potassium channel inhibitors had no effect on bupivacaine-induced relaxation in the endothelium-denuded aortas precontracted with phenylephrine, whereas verapamil or nifedipine attenuated bupivacaine-induced relaxation. The magnitude of the bupivacaine-induced relaxation was enhanced in the 100mM KCl-induced precontracted aortas compared with the phenylephrine-induced precontracted aortas. Verapamil attenuated the phenylephrine-induced contraction. The magnitude of the bupivacaine-induced relaxation was higher than that of the bupivacaine-induced $[Ca^{2+}]_i$ decrease in the aortas precontracted with phenylephrine. Conclusions: Taken together, these results suggest that toxic-dose bupivacaine-induced vasodilation appears to be mediated by decreased calcium sensitization in endothelium-denuded aortas precontracted with phenylephrine. In addition, potassium channel inhibitors had no effect on bupivacaine-induced relaxation. Toxic-dose bupivacaine-induced vasodilation may be partially associated with the inhibitory effect of voltage-operated calcium channels.

• 동의생리병리학회지
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• 제16권2호
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• pp.389-396
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• 2002

In the present work, we examined the mechanism of vasorelaxant effect of scopoletin, an active constituent of Artemisia capillaris on rat thoracic descending aortic rings. Scopoletin induced a concentration-dependent relaxation in rat thoracic descending aortic rings pre-contracted with phenylephrine (EC/sub 50/ = 238.94±37.4 μM), while it was less effective in rat thoracic descending aortic rings precontracted with high potassium solution (KCI 30 mM). Vasorelaxation by scopoletin was significantly inhibited after endothelial removal, but recovered at high concentration. Pretreatment of rat thoracic descending aortic rings with N/sup G/-nitro-L-arginine (100 μM), a nitric oxide synthase inhibitor, and atropine (1 μM), a muscarinic receptor antagonist, significantly inhibited scopoletin-induced relaxation of rat thoracic descending aortic rings. Neither indomethacin (3 μM), an inhibitor of cydooxygenase, nor propranolol (1 μM), a β -adrenoceptor antagonist, modified the effect of scopoletin. The combination of N/sup G/ -nitro-L-arginine (100 μ M) and miconazole (10 μ M), an inhibitor of cytochrome P 450, did not modify the effect of scopoletin, when compared with pretreatment with N/sup G/-nitro-L-arginine(100 μM) alone. Vasorelaxant effect of scopoletin was inverted by pretreatment with diltiazem (10 μM), a Ca/sup 2+/-channel blocker, at low concentration, while restored at high concentration. Apamin (K/sub ca/-channel blocker, 1 μM), 4-aminopyridine (4-AP, K/sub v/-channel blocker, 1 mM), and tetrodotoxin (TTX, Na/sup +/-channel blocker 1 μM) potentiated the vasorelaxant effect of scopoledn, but glibendamide (K/sub ATP/-channel blocker, 10 μM), tetraetylammonium(TEA, non-selective K-channel blocker, 10 mM) did not affect the relaxation of scopoletin. Free radical scavengers (TEMPO, catalase, mannitol) did not modify vascular tone. These results suggest that nitric oxide, Ca/sup 2+/ -channels play a role in endothelium-dependent relaxations to scopoletin in rat aortas, that apamin, 4-AP, TTX but not glibenclamide, TEA potentiated relaxation to scopoletin mediated by these channels, and that free radicals do not concern to the vasorelaxant effect of scopoletin.