내피세포를 제거한 흰쥐 대동맥에서 Phenylephrine이 일으킨 수축반응에 대한 alpha-수용체 길항제의 영향

홍승철(Sung Cheul Hong),강맹희(Maeng Hee Kang),박상일(Sang Il Park),박미선(Mi Sun Park),최수경(Su Kyung Choi),정준기(Joon Ki Chung),서석수(Suk Soo Suh) 대한약학회 1991 약학회지 Vol.35 No.5

The effects of an irreversible or a reversible alpha1-adrenoceptor antagonist (dibenamine or prazosin) on alpha1-adrenoceptor-mediated vasoconstrictions were studied in the endothelium-denuded rat aorta. In these experiments, the mobilization of intracelluler calcium and translocation of extracellular calcium were also studied. To exclude the modulation of endothelium releasing EDRF and EDCF, the endothelium was removed in all rat aortas. Contraction induced by phenylephrine (a full alpha1-adrenoceptor agonist) was separated into a fast phasic component of the response due to the release of intracellular calcium and a slow tonic one due to the influx of extracellular calcium. Pretreatments with increasing doses of reversible alpha1-adrenoceptor antagonist prazosin, as well as irreversible alpha1-adrenoceptor antagonist dibenamine, inhibited the phasic component of phenylephrine-induced contraction more effectively than the tonic one. Pretreatment of dibenamine (0.2 mcM) or prazosin (10 nM) to the rat aorta abolished phasic response but remained tonic one about 41% and 51%, respectively. These results suggest that as the efficiency of phenylephrine was progressively reduced by pretreatments with increasing doses of an irreversible or a reversible alpha1-adrenoceptor antagonist (dibenamine or prazosin), the contraction induced by phenylephrine became progressively more dependent on the influx of extracellular calcium.

가토 위저에서 Nitric oxide에 의해 매개되는 비-아드레날린 비-콜린성 이완반응

홍승철(Sung Cheul Hong),최지은(Ji Eun Choi),한석규(Suk Kyu Han),김영미(Young Mi Kim),김남득(Nam Deuk Kim),박미선(Mi Sun Park),홍은주(Eun Ju Hong),김진보(Jin Bo Kim) 대한약학회 1994 약학회지 Vol.38 No.2

The role of nitric oxide(NO) as neurotransmitter in non-adrenergic non-cholinergic (NANC) relaxation induced by electrical stimulation has been studied in circular muscle strips of the rabbit gastric fundus. In the presence of atropine and guanethidine, low frequency(1-20 Hz) and short trains (5 s) of electrical stimulation induced the frequency-dependent relaxations which were not affected by adrenergic and cholinergic blockage, but abolished by tetrodotoxin, a nerve conductance blocker. L-NNA, a stereospecific inhibitor of NO biosynthesis, inhibited the relaxations induced by electrical stimulation but not affected the relaxation to exogenous NO. The effect of L-NNA was prevented by L-arginine, the precursor of the NO biosynthesis, but not by its enantiomer, D-arginine. Exogenous administration of NO(10- 100 mcM) caused the concentration-dependent relaxation which showed a similarity to those obtained with electrical stimulation. Hemoglobin, a NO scavenger, abolished the NO-induced relaxations and also markedly inhibited those evoked by electrical stimulation. Application of adenosine triphosphate(l - 10 mcM) induced concentration-independent contractions, but in high dose caused temporary contraction followed by relaxation which was not affected by L-NNA. Exogenous vasoactive intestinal polypeptide(10-100 nM) induced the concentration-dependent relaxation, while its effects were slower in onset and more persistent than those induced by short trains and low frequencies of electrical stimulation. Based on above results, it is suggested that NO is the principal neurotransmitter of NANC nerve at relaxation induced by short trains and low frequencies of electrical stimulation in the rabbit gastric fundus.

오가피 에탄올 엑기스의 Guinea pig 회장수축작용에 관한 연구

홍승철(Sung-Cheul Hong),손병화(Byeng-Wha Shon) 한국생약학회 1980 생약학회지 Vol.11 No.1

오가피는 강장, 강정제로서 응용되고 있으며, 약리작용에 관해서는 Brekhmann 등에 의하여 체중증가작용, 동화작용, 노동력증가작용 및 항스트레스작용 등이 있음을 보고한 바 있다. 연자 등은 오가피의 약리작용을 연구하기 위한 일환으로서 오가피 에타놀 액기스(AEE)의 Guinea pig회장운동에 미치는 영향을 관찰하여 다음과 같은 결과를 얻었다. 1) AEE는 Guinea pig 회장에 대하여 현저한 수축작용이 있으며, 농도증가(3×10^-6∼10^(-3)g/ml)에 따라 수축작용이 증가되었다. 2) AEE의 회장수축작용은 atropine, diphenhydramine, methysergide, indomethacin, hexamethonium 및 morphine의 처리로 영향을 받지 않았으며, porcaine, La^(+++)에 의하여 억제되었다. 3) AEE의 회장수축작용은 Ca^(++)-free tyrode액으로 바꾸었을때 소실되었으며, 소량의 Ca^+을 주입했을 때 현저한 수축작용을 일으켰다.

토끼 음경해면체의 비-아드레날린 비-콜린성 이완반응에서 산화질소의 역할

박미선,김진보,홍은주,홍승철,Park, Mi-Sun,Kim, Jin-Bo,Hong, Eun-Ju,Hong, Sung-Cheul 대한약학회 1997 약학회지 Vol.41 No.3

The role of nitric oxide (NO) on the non-adrenergic non-cholinergic (NANC) relaxations induced by the short and prolonged electrical field stimulation (EFS) has been studied in the rabbit corpus cavernosum. In the presence of atropine and guanethidine the prolonged EFS (2-16 Hz) of corpus cavernosal strips precontracted with phenylephrine produced frequency-dependent relaxations, which were abolished by tetrodotoxin as shown in the relaxations induced gy the short EFS, indicating that their orgin is NANC nerve stimulation. $N^G$-nitro-L-arginine (L-NNA), inhibitor of nitirc oxide synthase, caused a concentration-dependent inhibition to the NANC relaxation, and at 100 M L-NNA the relaxation were virtually abolished. The inhibitory effect of L-NNA was reversed by L-arginine. Hemoglobin abolished the relaxations to NO and also caused a concentration-dependent inhibition of the NANC relaxation. The hemoglobin-resistant relaxation induced by EFS was eliminated by L-NNA. Methylene blue significantly reduced the NANC relaxation in a conentration-dependent manner. The NANC relaxation was not affected by a VIP-inactivating pepridase, alpha0chymotrypsin, whereas VIP-induced relaxation was completely abolished. NO- and VIP-induced relaxation were not affected by L-NNA. These results indicate that the NANC relaxation induced by prolonged EFS of the rabbit corpus cavernosum is mediated by NO-guanosine 3',5'-cyclic monophosphate pathway as shown in the relaxation induced by the short EFS, and that VIP release is not essential for the NANC relaxation of the rabbit corpus cavernosum and VIP is not involved the generation fo NO.

토끼 위 근위부의 비-아드레날린 비-콜린성 이완반응의 포타슘 체널에 의한 접합전 조절작용

홍은주(Eun Ju Hong),박미선(Mi Sun Park),박상일(Sang Il Park),김명우(Myung Woo Kim),최수경(Su Kyung Choi),홍승철(Sung Cheul Hong) 대한약학회 1997 약학회지 Vol.41 No.4

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, 3~30mcM) and tetraethylammonium (TEA, 100~1000mcM) 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 Ca2+-activated K+ channels, charybdotoxin and iberiotoxin, a blocker of small conduntance Ca2+-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, 1~30mcM) 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.

흰쥐 적출 대동맥에서 alpha1-수용체 효능약과 alpha2-수용체 효능약의 혈관수축반응에 대한 내피세포의 영향

정준기(Joon Ki Chung),홍승철(Sung Cheul Hong),최수경(Su Kyung Choi),강맹희(Maeng Hee Kang),구미경(Mi Geong Ku),박상일(Sang Il Park),윤일(Il Yun) 대한약학회 1990 약학회지 Vol.34 No.3

A comparison was made of the effects of selective alpha1-adrenoceptor agonist phenylephrine and selective alpha2-adrenoceptor agonist clonidine on endothelium-containing and endothelium-denuded rings of the rat aorta. In the case of phenylephrine, removal of endothelium increased sensitivity 2.5 fold at EC50 level and maximum contractive response 1.4 fold. In the case of clonidine, which gave only 15% of maximum contractive response given to phenylephrine on endothelium-containing rings, removal of the endothelium increased sensitivity 5.6 fold at EC50 level and maximum contractive response 5 fold, which was about 55% of that given by phenylephrine. In endothelium-denuded ring, phenylephrine-induced contraction tended to be more increased in tonic contraction than in phasic contraction as compared to that in endothelium-containing ring, while clonidine-induced contraction was monophasic and was increased only in tonic contraction. In the calcium-free solution or in the presence, of verapamil, contraction stimulated by clonidine was almost abolished while that stimulated by phenylephrine produced only phasic contraction. The depression of sensitivity to these agonists in rings with endothelium appeared to be due to the vasodepressor action of endothelium derived relaxing factor(EDRF), because hemoglobin, a specific blocking agent of EDRF, abolished this depression. It is unlikely that the endothelium-dependent relaxation was due to stimulation of release of EDRF, because clonidine did not produce endothelium-dependent relaxation in 5-hydroxytryptamine-precontracted ring even when its contractile action was blocked by the alpha1-adrenoceptor antagonist, prazosin. When the efficacy of phenylephrine was reduced to about the initial efficacy of clonidine by pretreatment with dibenamine, the contraction-response curves for phenylephrine became very similar to the corresponding curves obtained for clonidine before receptor inactivation. In the dibenamine-treated rings, contraction of phenylephrine was abolished in calcium-free solution or in the presence of verapamil like that obtained for clonidine before receptor inactivation. These results suggest that EDRF spontaneously released from endothelium depress contraction more profoundly in a case of an agonist with low efficacy and the phenylephrine-induced contraction was totally dependent on extracellular calcium as was that obtained for clonidine when the efficacy of phenylephrine was reduced to that of clonidine by irreversible inactivation of alpha1-adrenoceptor with dibenamine.

토끼 위체에서 비-아드레날린 비-콜린성 이완반응의 하행성 감소

홍은주(Eun Ju Hong),최지은(Ji Eun Choi),박미선(Mi Sun Park),김명우(Myung Woo Kim),최수경(Su Kyung Choi),홍승철(Sung Cheul Hong) 대한약학회 1997 약학회지 Vol.41 No.3

Non-adenergic non-cholinergic (NANC) innervation on the circular muscle of the rabbit gastric body was investigated by observing the magnitudy of relaxations induced by the electrical field stimulation (EFS). Strips were cut from the greater curvature of the gastric body and stimulated with 5s trains of 0.5 ms pulses at 1-20 Hz, 40 V. The EFS induced transient frequency-dependent contractons, followed by a slowly recovering relaxation ewpecially at higher frequency of the EFS. In the presence of atropine and guanethidine, the contractions were virtually abolished, while the frequency-dependent relaxations by the EFS remained unaffected. The magnitude of relaxations progressively decreased as the location of the strips gets closer to the bottom of the gastric body. The relaxations were ablished by tetrodotoxin, indicating that their orgin is the NANC nerve stimulation. NG-nitro-L-arginine (L-NNA, 10-100 mcM), the inhibitor of nitric oxide (NO)-synthase, caused a concentration-dependent inhibition of the NANC relaxations. The inhibitory effects of L-NNA were not affected gy the location of the strips and were reversed by L-arginine, the precursor of NO-biosynthesis. Hemoglobin (20-60 mcM), a NO scavenger, inhibited the NANC relaxation s in a concentration-dependent manner. This inhibition was more prominent in the NANC relaxations observed in the lower portion of the gastric body and the relaxations induced ly lower frequencies of the EFS. Methyelne blue (10-100 mcM), an inhibitor of cytosolic guanylate cyclase, markedly inhibited the NANC relaxations, almost abolishing the response at a higher dose (100mcM). These results suggest that NANX innervation of the rabbit gastric body progeressively decrease as he location of the strips gets closer to the bottom of the gastric body, and that the NANC relaxation is primarily mediated by NO-guanosine 3'',5''-cyclic monophophate (cyclic GMP).