• 대한약리학회지
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• 제11권2호
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• pp.29-40
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• 1975

1. 척수가토(脊髓家兎)에서 nicotine, DMPP, McN-A-343, AHR-602, tyramine, angiotensin및 neostigmine에 의한 심박증가(心搏增加)의 작용점(作用點)을 조사(調査)하였다. 2. 상기약물(上記藥物)에 의한 심박증가(心搏增加)는 reserpine 처리가토(處理家兎)에서는 대단히 약(弱)하였고, Propranolol 투여후(投與後)에는 거의 나타나지 않았다. 3. Tetrodotoxin, guanethidine은 isoproterenol, nicotine, DMPP, tyramine에 의한 심박증가(心搏增加)에는 영향(影響)을 미치지 않았으나 McN-A-343, AHR-602, angiotensin, neostigmine에 의한 심박증가(心搏增加)는 이를 현저(顯著)히 약화(弱化)시켰다. 4. Nicotine, DMPP의 심박증가(心搏增加)는 chlorisondamine으로 McN-A-343, AHR-602의 심박증가(心搏增加)는 atropine으로 각각(各各) 억제(抑制)되었다. 5. Isoproterenol, nicotine, DMPP, McN-A-343, tyramine, angiotensin, neostigmine은 적당량(適當量)을 우심방내(右心房內)에 주입(注入)하였을때 이들을 이정맥내(耳靜脈內)에 주사(注射)하였을 때와 비슷한 반응(反應)을 일으킬 수 있었다. 그러나 AHR-602 우심방내(右心房內) 주입(注入)은 유의(有意)한 심박증가(心搏增加)를 일으키지 않았다. 6. Nicotine, DMPP, neostigmine은 우심방내(右心房內) 주입시(注入時)는 현저(顯著)한 심박증가(心搏增加)를 일으켰으나, 동량(同量)을 우심실내(左心室內)에 주입(注入)하였을때는 증가(增加)를 일으키기 않았다. Isoprotereool 및 tyramine에 대한 반응(反應)은 우심실내(右心室內) 주입(注入)보다도 우심방내(右心房內) 주입시(注入時) 훨씬 컸다. 7. McN-A-343, angiotensin의 우심실내(右心室內) 주입시(注入時)는 우심방내(右心房內) 주입시(注入時)보다도 훨씬 현저(顯著)한 심박증가(心搏增加)를 일으켰고, AHR-602의 우심실내(左心室內) 주입(注入)도 현저(顯著)한 반응(反應)을 일으켰다. 8. Nicotine, DMPP, tyramine은 심장(心臟)의 aenergic nerve의 말단(末端) 또는 extraneuronal norepinephrine-store에 작용(作用)하여, Mcn-A-343, AHR-602, angiotensin은 심장(心臟)의 adrenergic nerve에 작용(作用)하여 심박증가(心搏增加)를 일으키며, nicotine, DMPP, tyramine, neostigmine의 작용점(作用點)은 주(主)로 우심방(右心房)에 McN-A-343, AHR-602, angiotenisin의 작용점(作用點)은 주(主)로 우심실(右心室)에 존재(存在)하는것으로 추론(推論)하였다.

• 대한수의학회지
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• 제43권3호
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• pp.405-414
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• 2003

The purpose of this study was to assess the role of tachykinins (TK) in mediating nonadrenergic noncholinergic (NANC) contractions produced by electrical field stimulation (EFS) in the longitudinal muscle of the rat ileum. In the presence of atropine ($1{\mu}M$), guanethidine ($5{\mu}M$), and L-nitroarginine (L-NNA, $200{\mu}M$), EFS (0.5ms pulse duration, 120 V, 1-20 Hz for 2 min) produced a frequency-dependent slowly-developing tonic contraction with superimposed phasic contractions ('on'-contraction) followed by off slowly-decreasing tonic and superimposed phasic contractions ('off'-contraction) of mucosa-free longitudinal oriented muscle strip. These EFS induced responses were blocked by tetrotoxin. $NK_1$ receptor selective antagonist L-732,138 strongly inhibited the EFS-induced excitatory responses. However $NK_2$ receptor selective antagonist, GR 159897 and $NK_3$ receptor selective antagonist SB 222200 did not significantly inhibited the responses. $NK_1$ receptor selective agonist [$Sar^9$,$Met(O_2)^{11}$] Substance P and $NK_2$ receptor selective agonist [${\beta}-Ala^8$]-neurokinin A (4-10) induced tonic contraction with superimposed phasic contractions of longitudinal oriented muscle strip and almost blocked by selective antagonist L-732,138 and GR 159897, respectively. But $NK_3$ receptor selective agonist senktide did not showed any effect. Nifedipine ($1{\mu}M$) abolished the contraction produced either by EFS or by the TK receptor agonists [$Sar^9$,$Met(O_2)^{11}$] Substance P or [${\beta}-Ala^8$]-neurokinin A (4-10). It is concluded that, in the longitudinal muscle of rat ileum, both $NK_1$ and $NK_2$ receptors modulated the responses to exogenous tachykinins, whereas $NK_1$ is mainly involved in NANC neuromuscular contraction.

• 대한약리학회지
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• 제19권2호
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• pp.25-34
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• 1983

가토의 문맥 절편에서 비 코린성-비 아드레나린성 이완반응에 대한 약리학적 성질을 규명하여 다음과 같은 결과를 얻었다. 1) 가토 문맥 절편에 있어서 비 코린성-비 아드레나린성 전기자극반응은 자극빈도의 증가에 따라 예민하게 증가하였으며, $Ca^{++}$에 이하여 크게 영향을 받았고, $Ca^{++}$농도를 달리하고 ATP를 첨가하여 이완반응은 일어났으나 이는 전극자극에 의한 반응에는 영향을 주지 아니하였다. 2) ATP, ADT 및 adenosine에 대한 반응은 용량에 의존하여 이완반응은 보였으나 자극에 의한 반응에는 크게 영향을 미치지 아니하였다. 3) Quinine과 isobutyl-methyl xanthine을 투여하였을 때 용량에 따라 긴장도의 하강을 나타내었을 뿐 이완반응은 길항하지 아니하였다. 4) 4-AP, $1{\mu}g/ml$존재하에서 전기자극에 대한 이완반응 폭은 서서히 증가하였고 대량의 4-AP에 의하여 는 긴장도가 하강하였다. 5) 4-AP반복투여후의 전기자극에 이한 반응은 대조군과 비교하여 큰 변화가 없었으나, adenosine을 반복투여하였을 때는 대조군에 비하여 증가를 나타내었다. 6) $^3H-purine$의 유출은 전기자극에 의하여는 경미하나 ATP나 adenosine투여로 현저히 증가하였으며, 4-AP, TTX 및 adenosine 반복투여후에도 $^3H-efflux$의 변동을 나타내지 아니하였다.

• 약학회지
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• 제41권3호
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• pp.389-398
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• 1997

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 elec trical 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-$100{\mu}M$), 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-$60{\mu}M$), 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-$100{\mu}M$), an inhibitor of cytosolic guanylate cyclase, markedly inhibited the NANC relaxations, almost abolishing the response at a higher dose ($100{\mu}M$). 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).

• 약학회지
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• 제38권2호
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• pp.149-157
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• 1994

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$(1{\sim}20\;Hz)$ and short trains (5s) 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$(10{\sim}100\;{\mu}M)$ 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$(1{\sim}10\;{\mu}M)$ 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$(10{\sim}100\;nM)$ 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.

• The Korean Journal of Physiology
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• 제26권1호
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• pp.55-68
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• 1992

The effects of changes in extracellular $Na^+\;and\;Ca^+$ concentration on the membrane potential and contractility were studied in the antral circular muscle of guinea pig stomach in order to elucidate the existence and the nature of $Na^+/Ca^{2+}$ exchange mechanism. All experiments were performed in tris buffered Tyrode solution which was aerated with 100% $O_2$ and kept at $35^{\circ}C.$ The treatment of $10^{-5}$ ouabain was performed to induce intracellular $Na^+$ loading prior to the start of experiment. The results were as follows: 1. $Na^+$-free Tyrode or high $Ca^{2+}$-Tyrode solution hyperpolarized the membrane potential and induced contracture. The time course of contracture was similar to that of change in membrane potential. 2. The degree of hyperpolarization and the amplitude of contracture decreased in accordance with the increase of extracellular $Na^+$ concentration. 3. $Na^+$-free contracture was developed even after blocking the influence of intrinsic nerves by the pretreatment with atropine, guanethidine and TTX. 4. $Ca^{2+}$-channel blockers(D-600 or $Mn^{2+}$) and the blocker of intracellular $Ca^{2+}$ release from sarcoplasmic reticulum(ryanodine) did not suppress the development of $Na^+$-free contracture. And also, dinitrophenol had no effect on $Na^+$-free contracture. 5. Dose-response relationship between extracellular $Na^+$ concentrations and the magnitude of contractures showed a sigmoid pattern. The slope of straight line from Hill plot was 2.7. 6. In parallel with the increase of extracellular $Ca^{2+}$ concentration, the amplitude of contracture increased dose dependently and was maximum at 8 mM $Ca^{2+}$-Tyrode solution. 7. The relationship between extracellular $Ca^{2+}$ concentrations and the magnitude of contractures showed hyperbolic pattern. The slope of straight line from Hill plot was 1.1. From the above results, it is suggested that $Na^+/Ca^{2+}$ exchange mechanism exists in the antral circular muscle of guinea pig stomach and this mechanism affects the membrane potential electrogenically.

• The Korean Journal of Physiology and Pharmacology
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• 제3권2호
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• pp.165-174
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• 1999

We explore the question of whether adenosine 5'-triphosphate (ATP) acts as an excitatory neurotransmitter in guinea-pig gastric smooth muscle. In an organ bath system, isometric force of the circular smooth muscle of guinea-pig gastric antrum was measured in the presence of atropine and guanethidine. Under electrical field stimulation (EFS) at high frequencies (＞20 Hz), NO-mediated relaxation during EFS was followed by a strong contraction after the cessation of EFS (a 'rebound-contraction'). Exogenous ATP mimicked the rebound-contraction. A known $P_{2Y}-purinoceptor$ antagonist, reactive blue 2 (RB-2), blocked the rebound-contraction while selective desensitization of $P_{2Y}-purinoceptor$ with ${\alpha},{\beta}-MeATP$ did not affect it. ATP and 2-MeSATP induced smooth muscle contraction, which was effectively blocked by RB-2 and suramin, a nonselective $P_2-purinoceptor$ antagonist. Particularly, in the presence of RB-2, exogenous ATP and 2-MeSATP inhibited spontaneous phasic contractions, suggesting the existence of different populations of purinoceptors. Both the rebound-contraction and the agonist-induced contraction were not inhibited by indomethacin. The rank orders of agonists' potency were 2-MeSATP > ATP ${ge}$ UTP for contraction and ${\alpha},{\beta}-MeATP\;{\ge}\;{\beta},{\gamma}-MeATP$ for inhibition of the phasic contraction, that accord with the commonly accepted rank order of the classical $P_{2Y}-purinoceptor$ subtypes. Electrical activities of smooth muscles were only slightly influenced by ATP and 2-MeSATP, whereas ${\alpha},{\beta}-MeATP$ attenuated slow waves with membrane hyperpolarization. From the above results, it is suggested that ATP acts as an excitatory neurotransmitter, which mediates the rebound-contraction via $P_{2Y}-purinoceptor$ in guinea-pig gastric antrum.

• The Korean Journal of Physiology and Pharmacology
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• 제1권3호
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• pp.303-313
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• 1997

The role of the lower esophageal sphincter(LES) is characterized by the ability to maintain tone and to relax allowing the passage of a bolus. It is known that LES relaxation during swallowing may be induced by the cessation of the tonic neural excitation and the activation of non-adrenergic, non-cholinergic(NANC) inhibitory neurons. Furthermore, it is generally accepted that the relaxation of the smooth muscle is mediated primarily by the elaboration of adenosine 3',5'-cyclic monophosphate(cyclic AMP) and guanosine 3',5'-cyclic mono-phosphate(cyclic GMP) via activation of adenylate cyclase and guanylate cyclase, respectively. It is thus possible that cyclic nucleotides might be a second messenger involved in neural stimulation-induced relaxation of LES, although a relationship between relaxation and changes in cyclic nucleotides after neural stimulation has not been established. The present study was performed to define the participation of cyclic nucleotides in the relaxation of LES of dog in response to neural stimulation. Electrical field stimulation(EFS) caused relaxation of the canine isolated LES strips in a frequency-dependent manner, which was eliminated by pretreatment with tetrodotoxin$(1{\mu}M)$, but not by atropine$(100{\mu}M)$, guanethidine$(100{\mu}M)$ and indomethacin$(10{\mu}M)$. The nitric oxide synthase inhibitors, $N^G-nitro-L-arginine$, $N^G-nitro-L-arginine$ methyl ester and $N^G-monomethyl-L-arginine$ inhibited EFS-induced relaxation. Additions of sodium nitroprusside, a nitrovasodilator and forskolin, a direct adenylate cyclase stimulant, caused a dose-dependent relaxation of LES smooth muscle. Effects of sodium nitroprusside and forskolin were selectively blocked by the corresponding inhibitors, methylene blue for guanylate cyclase and N-ethylmaleimide(NEM) for adenylate cyclase, respectively. Dibutyryl cyclic AMP and dibutyryl cyclic GMP caused a concentration-dependent relaxation of the LES smooth muscle tone, which was not blocked by NEM or methylene blue, respectively. However, both NEM and methylene blue caused significant antagonism of the relaxation in LES tone in response to EFS. EFS increased the tissue cyclic GMP content by 124%, whereas it did not affect the tissue level of cyclic AMP. Based on these results, it is suggested that one of the components of canine LES smooth muscle relaxation in response to neural stimulation is mediated by an increase of cyclic GMP via the activation of guanylate cyclase. Additionally, an activation of cyclic AMP generation system was, in part, involved in the EFS-induced relaxation.

• 대한수의학회지
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• 제37권1호
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• pp.119-128
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• 1997

The relaxation of gastric fundus smooth muscles is the primary physiological event which induces the receptive relaxation of monogastric animals. L-arginine/Nitric oxide(L-arg/NO) system is known to mediate the inhibitory non-adrenergic non-cholinergic(NANC) neurotransmission in various tissues including gastrointestinal smooth muscles. The longitudinal smooth muscles of porcine gastric fundus showed fast relaxation during electrical field stimulation(EFS) and rebound contraction after EFS in NANC condition. So, the purpose of present study was elucidation of the neurotrasmitters related to the NANC relaxation and explanation of the relation between NANC relaxation and L-arg/NO system. The longitdinal smooth muscles of porcine gastric fundus were hung in the organ bath and under the presence of guanethidine($5{\times}10^{-5}M$), precontraction was induced by carbachol($1{\times}10^{-6}M$). The muscle responses to EFS and drugs were isomerically recorded. The rusults were summarized as follows. 1. The longtudinal muscles of porcine gastric fundus showed frequency-dependent relaxation and rebound contraction to electrical field stimulaton(1ms, 8V, 1~16Hz, 20sec, EFS). These responses were blocked by tetrodotoxin($1{\times}10^{-6}M$). 2. The relaxation and rebound contraction of the longitudinal muscles of porcine gastric fundus to EFS were inhibited by L-NAME($2{\times}10^{-5}M$). The inhibitory effect of L-NAME was antagonized by L-arginine($1{\times}10^{-3}M$), but not by D-arginine($1{\times}10^{-3}M$). 3. Exogenous NO($NaNO_2$, $1{\times}10^{-5}{\sim}1{\times}10^{-4}M$, pH=2.0) caused concentration-dependent relaxation as EFS did. 4. Methylene Blue($2{\times}10^{-5}M$), a soluble guanylate cyclase inhibitor, inhibited the relaxation and rebound contraction of the longitudinal muscles of porcine gastric fundus induced by EFS, but N-ethlmaleimide, a adenylate cyclase inhibitor, did not. 5. 8-Br-cGMP($1{\times}10^{-6}{\sim}3{\times}10^{-6}M$), permeable cGMP analogue, induced dose-dependent relaxation. but 8-Br-cAMP($1{\times}10^{-6}{\sim}3{\times}10^{-6}M$), permeable cAMP analogue, did not. Both did not evoked rebound contraction. 6. ${\alpha}$-chymotrypsin did not affect the relaxation of the longitudinal muscles of porcine gastric fundus. 7. Reactive blue 2($1{\times}10^{-4}M$, 40min) siginificantly inhibited the rebound contraction induced by EFS and inhibited contraction caused by exogenous ATP($1{\times}10^{-4}{\sim}1{\times}10^{-3}M$). These results suggests that NANC relaxation of the longitudinal muscles of porcine gastric fundus mainly mediated by NO and the rebound contraction is related to NO and other neurotransmitters.