• 대한약리학회지
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• 제2권1호
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• pp.71-82
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• 1966

The inhibitory effect of 5-hydroxytryptamine (5-HT) on the isolated intestinal strips of the tortoise (Amyda japonica), rat, rabbit and guinea pig was investigated. 1) The strips from the middle or lower part of the tortoise intestine responded with relaxation to 5-HT $(10^{-9}{\sim}10^{-5}g/ml)$, and the magnitude of the relaxation was proportional to the dose of 5-HT. The rectal part of the tortoise intestine, in contrast, showed contraction, the magnitude of which also was proportional to the dose of 5-HT. 2) Various blocking agents such as methysergide, morphine, tetracaine, nethalide, bretylium, hexamethonium, mecamylamine and chlorisondamine, showed no selective blocking activity on the relaxant effect of 5-HT on the tortoise intestine. The inhibitory effect of isoproterenol on the tortoise intestine, however, was selectively blocked by nethalide, and the stimulatory effect of 5-HT on the rectal part of the tortoise was blocked by methysergide. 3) In the presence of 5-HT, the stimulatory effect of DMPP on the tortoise intestine was remarkably attenuated, whereas that of acetylcholine and $BaCl_2$ was little affected. In the presence of isoproterenol, the stimulatory effect of acetylcholine and $BaCl_2$ were affected, but that of DMPP was little affected. 4) Large dose of 5-HT($10^{-4}$g/ml) produced inhibitory effect on the strips from the distal part of the isolated colon of the rat, rabbit and guinea pig, when the strips had been exposed to 5-HT($10^{-4}$g/ml), methysergide or phen`oxybenzamine. 5) Bretylium, as well as nethalide, abolished or remarkably reduced, in a few cases of the experiments, the inhibitory effect of the large dose of 5-HT on the distal part of the colon, whereas morphine did not affect it. 6) The ileal strips of the guinea pig also showed relaxation, as in the colonic strips, having been exposed to the large dose of 5-HT or phenoxybenzamine. This effect, however, was not obsered in the case of the rabbit ileum. 7) The property of the action-site of 5-HT in the tortoise intestine seemd to be different from the 5-HT receptors which have been revealed by several investigators. 8) Adrenergic component seemed to be participated in the inhibitory effect of 5-HT on the colon of the rat and rabbit.

• The Korean Journal of Physiology
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• 제13권1_2호
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• pp.41-50
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• 1979

The activation mechanism of K-induced contracture was studied in renal vascular muscle which does not generate an action potential readily and in taenia coli which generates a spike potential spontaneously. Helical strips of arterial muscle from rabbit renal arteries and longitudinal strips of taenia coli from guinea-pig's colons, respectively, were prepared. All experiments were performed in Tris-buffered Tyrode solution which was aerated with 100% $O_2$ and kept $35^{\circ}C$. Renal arterial muscles developed the contracture rapidly, which was composed of a small phasic and a large tonic components, when exposed to a 40 mM K-Tyrode solution. In the absence of external $Ca^{++}$, however, no K-contracture appeared. The contracture induced by K-depolarization was abolished by the treatment with verapamil, which is known to be a selective $Ca^{++}-blocker$ through potential-sensitive $Ca^{++}-channel$. K-contracture of taenia coli showed the contracture composed of a large phasic and a small tonic components. In the $Ca^{++}-free$ Tyrode solution, only the tonic component was abolished and almost no change in the phasic component was observed. The amplitude of tonic component was dependent on the external $Ca^{++}$; The tonic component increased dose-dependently by a stepwise increase of the external $Ca^{++}$, and this component decreased in parallel with the increase of verapamil in the external medium. The results of this experiment suggest that K-contracture of rabbit renal artery is the direct result of the influx of the external $Ca^{++}$, while that of taenia coli is the result of both $Ca^{++}$ influx and the release of sequestered $Ca^{++}$.

• Archives of Pharmacal Research
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• 제18권2호
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• pp.121-128
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• 1995

The role of nitric oxide (NO) in non-adrenegic non-cholinergic (NANC) neurotransmission was studied on circular muscle strips of the dorsal part of the fuinea-pig gastric fundus. In the presence of atropine and guanethidine, a low frequency-dependent relaxsations which were not affected by adrenergic and cholinergic blockage but abolished by tetrodotoxin. $N^G$-nitro-L-arginine (L-NNA), a stereospecific inhibitor of NO-biosynthesis, inhibited the relaxations induced by electrical stiumulations but not the relaxations to exogenous nitric oxide. The effect of L-NNA was prevented by L-arginine, the precursor of the NO biosynthesis but not by its enantiomer, D-arginine. Exgenous administration of No caused concentration -dependent relaxations which showed a similarity to those obtained with electrical simultaion. Hemoglobin, a NOscavenger, abolished the NO-induced relaxations and also markedly reduced those induced by electrical simultaion. The inhibitory effect os hemoglobin was similar to that of L-NNA. Application of ATP caused weak relaxations compared with those to electrical stimultaion, which were unaffected by L-NNA. Exogenously applied vasoactive intestinal polypeptide (VIP) induced concentration-dependent relaxation which was not affected by L-NNA. These results suggest that NO is produced and released mainly as a neurotransmitter from enteric neurons during NANC relaxation induced by low frequencies and short trains of electrical simulation and has a main role in NANC neurotransmission at relaxation induced by these electrical simultaions in the guinea-pig gastric fundus.

• Biomolecules & Therapeutics
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• 제7권3호
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• pp.278-284
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• 1999

DK1001 is a thebain derivative, which is newly synthesized as an alkaloid analgesic. This study was designed to study effects of DK1001 on the ligands binding to the opioid receptor subtypes, and general pharmacology of DK1001. DK1001 inhibited the binding of [$^3H$]DAMGO, a selective mu-subtype agonist, to the opioid receptor of rat forebrain in a concentration-dependent manner. $EC_{50}$ of DK1001 was significantly lower than that of morphine. DK1001 inhibited the binding of 〔$^3$H〕DPDPE, a selective delta-subtype agonist concentration-dependently. DK1001(0.5 mg/kg) had no effects on behavior, body temperature, blood pressure. respiratory rate, and intestinal charcoal propulsion of mice. In addition, DK1001 did not affect on the contractilities of isolated muscle strips of aorta, ileum, and trachea of rats. These results suggest that DK1001 might be a potent analgesic without serious side effects.

• Parasites, Hosts and Diseases
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• 제30권2호
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• pp.91-100
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• 1992

폐홉충의 생리식염수 추출액 내에 있는 여러 가지 성분 단백질의 생화학적 성상, 면역학적 특징 그리고 충체 내에서의 생성위치 등의 단세포군 항체나 전기영동을 이용한 연구에서 일부 밝혀졌다. 이 실험은 폐흡충 성충의 생리식염수 추출액 내에 있는 각 성분단백질이 폐흡충의 어느 부위에서 유래한 것인지를 알기 위하여 실시하였다. 먼저 생리식염수 추출액을 8% disc-PAGE로 전기영동하여 성분단백질을 분리하고 각 단백질 대(대)를 포함하는 젤을 잘라 내었다. 이어 전기영동으로 젤에서 성분단백질을 용출(용출)하였다. 각각의 단백질을 토끼에 면역시켜 성분 단백질별 항폐흡충 면역혈청을 만들고 이 항혈청으로 폐흡충 및 감염 고양이 폐의 절편에 면역효소 염색법을 시행하였다. 그 결과 성충추출액으로 면역한 항폐흡충 면역혈청은 폐흡충 성충의 충란, 장관상피세포, 장관 내용물에 강한 반응을 보였고 실질조직에도 염색이 되었다. 그러나 표피, 표피하세포, 고환, 흡판등은 반응이 없었다. 1번 Band 단백질의 항혈청은 충란내 세포에 염색이 되었고 충체에서 배출되어 폐실질 조직에 들어있는 충란에 더욱 강하게 반응하였다. 2번 Band 단백질의 항혈청은 폐홉충의 실질조직에 반응하였다. 3번 Band 단백질의 항혈청은 2번 Band 단백질과 교차반응을 일으켜 염색 반응을 관찰하지 않았다. 4번 Band 단백질의 항혈청은 폐흡충의 장관 내용물과 강한 반응을 보였고 5번 Band 단백질의 항혈청은 장관상피세포에 반응하였다. 6/7번 Band 단백질과 8번 나and 단백질의 항혈청은 각각 실질조직에 반응하였다.

• 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 and Pharmacology
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• 제4권3호
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• pp.227-234
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• 2000

Many reports suggest that neurotensin (NT) in the gastrointestinal tract may play a possible role as a neurotransmitter, a circulating hormone, or a modulator of motor activity. NT exerts various actions in the intestine; it produces contractile and relaxant responses in intestinal smooth muscle. This study was designed to investigate the effect of NT on motility of antral circular muscle strips in guinea-pig stomach. To assess the role of $Ca^{2+}$ influx in underlying mechanism, slow waves were simultaneously recorded with spontaneous contractions using conventional intracellular microelectrode technique. At the concentration of $10^{-7}$ M, where NT showed maximum response, NT enhanced the magnitude $(863{\pm}198%,\;mean\;SEM,\;n=13)$ and the frequency $(154{\pm}10.3%,\;n=11)$ of spontaneous contractions. NT evoked a slight hyperpolarization of membrane potential, tall and steep slow waves with abortive spikes $(278{\pm}50%,\;n=4).$ These effects were not affected by atropine $(2\;{\mu}M),$ guanethidine $(2\;{\mu}M)$ and tetrodotoxin (0.2μM). NT-induced contractile responses were abolished in $Ca^{2+}-free$ solution and reduced greatly to near abolition by $10\;{\mu}M$ of verapamil or 0.2 mM of $CdCl_2.$ Verapamil attenuated the effects of NT on frequency and amplitude of the slow waves. Taken together, these results indicate that NT enhances contractility in guinea-pig gastric antral circular muscle and $Ca^{2+}$ influx through the voltage-operated $Ca^{2+}$ channel appears to play an important role in the NT-induced contractile mechanism.

• 약학회지
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• 제41권3호
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• pp.370-380
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• 1997

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.

• The Korean Journal of Physiology and Pharmacology
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• 제3권3호
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• pp.275-282
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• 1999

Muscle strips and muscle cells from cat stomach were used to investigate whether spontaneously formed cyclic nucleotides were involved in the inhibition of gastric smooth muscle contraction. A phosphodiesterase inhibitor, 3-isobutyl-1-methylxanthine (IBMX), increased the levels of both cyclic GMP (cGMP) and cyclic AMP (cAMP) in resting state cells, while decreasing acetylcholine-induced muscle contraction. Under the influence of IBMX, SQ22536, an adenylyl cyclase inhibitor and methylene blue, a guanylyl cyclase inhibitor completely blocked increases in cAMP and cGMP respectively, without any effect on contraction. However, the combination of SQ22536 and methylene blue completely blocked increases in both cAMP and cGMP levels and stimulated contractions markedly even in the presence of IBMX. Muscle contraction inhibitors such as isoprenaline, vasoactive intestinal polypeptide and sodium nitroprusside also appeared to increase cyclic nucleotide levels which decreased contraction. Which nucleotide increased the most was dependent on the agonist used. Therefore, irrespective of the cyclic nucleotide class, the spontaneous formation of cyclic nucleotides should be considered in evaluating the mechanism of gastric smooth muscle relaxation.

• The Korean Journal of Physiology
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• 제20권1호
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• pp.125-133
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• 1986

Ethanol이 고양이 회장 종주근의 수축에 미치는 영향을 관찰한 결과 정상 Tyrode용액에서는 $0.5{\pm}4%$ 범위내에서 자발적 수축 및 기초장력을 억제하였으나 $Na^+$이 surcose로 대치된 용액에서는 수축을 유발시켰다. 이러한 수축은 ethanol의 농도에 비례하여 증가하였으며 용액내의 Na-free 용액으로 처리한 기간이 길수록 증가하였다. 용액내 $Ca^{2+}$이 없는 경우에도 ethanol에 의한 수축은 $La{+3}$에 의해 억제되었으나 verapamil을 전처치한 후 Na-free액을 처리했을 때는 수축이 나타나지를 않았다. Ethanol은 $^45Ca$의 유출에는 어떤 영향을 나타내지는 못하였다. 이상의 결과로 보아 Na-free용액에서 ethanol은 세포막에 결합하고 있는 $Ca^{2+}$이나 세포내부에 결합하고 있는 $Ca^{2+}$의 세포내로 유리를 증가시켜 수축을 유발시키는 것으로 사료된다.