• 제목/요약/키워드: Desensitization

검색결과 121건 처리시간 0.037초

Effect of Ca2+ on contractile responses induced by perivascular nerve stimulation in isolated coronary artery of pig

  • Hong, Yong-geun;Shim, Cheol-soo;Kim, Joo-heon
    • 대한수의학회지
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    • 제39권4호
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    • pp.702-709
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    • 1999
  • The present study was performed to elucidate the effects of extracellular $Ca^{2+}$ on contractile responses in isolated porcine coronary artery ring using by perivascular nerve stimulation (PNS). Especially, the study was focused on the source of $Ca^{2+}$ on $P_{2X}$-purinoceptor mediated muscle contraction which one of $P_2$-purinoceptor subtypes. The following results can be drawn from these studies : 1. The phasic contractions induced by PNS were inhibited with muscarinic receptor antagonist, atropine ($10^{-6}M$). 2. The phasic contractions induced by PNS were significantly inhibited by sequential treatment with atropine and adrenergic neural blocker, guanethidine ($10^{-6}M$). 3. The phasic contractions induced by PNS were inhibited with $P_{2X}$-purinoceptor desensitization by repetitive application of $\alpha$,$\beta$-Me ATP ($10^{-4}M$). 4. The phasic contractions induced by PNS were so weakened in calcium-free medium. 5. The phasic contractions induced by PNS were inhibited with calcium channel blocker, verapamil ($10^{-6}{\sim}5{\times}10^{-6}M$). 6. The phasic contractions induced by PNS on pretreated with verapamil ($10^{-6}{\sim}5{\times}10^{-6}M$) were not changed by $\alpha$,$\beta$-Me ATP ($10^{-4}M$). These results demonstrate that the neurogenic phasic contractions induced by PNS are due to adrenergic-, cholinergic- and $P_{2X}$-purinergic receptors and the origin of $Ca^{2+}$ on $P_{2X}$-purinoceptor mediated muscle contraction is extracellular $Ca^{2+}$ through plasmalemmal $Ca^{2+}$ channels.

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돼지 방광 평활근에 있어서 P2X-purinoceptor의 작용 (Action of P2X-purinoceptor on urinary bladder smooth muscle of pig)

  • 박상은;홍용근;심철수;전석철;김주헌
    • 대한수의학회지
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    • 제37권1호
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    • pp.103-110
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    • 1997
  • The experiments were carried out to elucidate the relationships between neurogenic effects of electrical transmural nerve stimulation and effect of adenosine 5'-triphosphate(ATP) to purinoceptor on the urinary bladder smooth muscle of pig. The results were as follows : 1. The contractile responses induced by electrical transmural nerve stimulation(10V or 20V, 0.5msec, 10sec) were the frequency(2~64Hz) dependent manner. 2. The contractile response induced by carbachol was responsed with a dose-dependent manner and the maximum contractility was $10^{-4}M$. 3. The contractile responses induced by ATP were increased in a dose-dependent manner ($10^{-5}{\sim}10^{-3}M$). 4. The contractile response induced by electrical transmural nerve stimulation(10V, 2~32Hz, 0.5msec, 10sec) was partially blocked by the treatment with atropine($10^{-5}M$), and was powerfully inhibited by 3 times of addition with ATP($10^{-5}M$). 5. The contractile response induced by electrical transmural nerve stimulation(10V, 2~32Hz, 0.5msec, 10sec) was partially blocked by the treatment with atropine($10^{-5}M$), and was completely blocked by the desensitization of the $P_{2X}$-purinoceptor using ${\alpha}$, ${\beta}$-methylene ATP($5{\times}10^{-5}M$). These results suggest that purinergic nerve was innervated, and ATP and acetylcholine was released by the electrical transmural nerve stimulation in urinary bladder smooth muscle of pig.

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Escherichia coli에 의한 방향족 아미노산 생산에 관한 연구 (A Study on the Production of Aromatic Amino Acids by Escherichia coli.)

  • Park, Young-Jin
    • 한국미생물·생명공학회지
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    • 제13권2호
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    • pp.119-127
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    • 1985
  • 여러 가지 Escherchia coli 변이주의, glucose 와 ammonium염과 같은 간단한 기질로부터 방향족 아미노산 특히 phenylanine을 생합성하는 능력을 비교 검토한 결과 방향족 아미노산 생합성과정중 common pathway의 첫 번째 반응이 phenylanine 생합성에 가장 큰 영향을 준다는 것을 확인하였다. 따라서 관계효소인 DAHP synthase의 효소활성과 생합성에 관련된 각종 대사 제어작용을 효과적으로 제거시킴으로서 phenylalanine 생산량을 크게 높일 수 있었으며 더욱이 phenylalanine terminal pathway의 첫 단계 반응을 촉매하는 prephenate de-hydratase의 효소활성과 효소생합성에 관련된 제어 작용도 동시에 제거하면 phenylalanine생산이 상승적으로 증가됨을 보였다. 한편 방향족아미노산의 transport system에 관계하는 arop유전자의 변이는 phenylalanine생산을 크게 저하시키는 효과를 나타내었다.

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Agonist-induced Desensitization of Muscarinic Acetylcholine Receptor in Rat Brain

  • Lee, Jong-Hwa;Esam-E.El-Fakahany
    • Archives of Pharmacal Research
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    • 제10권4호
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    • pp.212-218
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    • 1987
  • Intact brain cell aggregates were dissociated from adult rat brains without cerebellum using a sieving technique. This proparation was used to elucidate the binding characteristics of agonist to muscarinic acetylcholine receptors (mAchR) in brain. Incubation of cells with carbamylcholine (carbachol) was shown agonist-induced receptor down-regulation depending on the concentration of agonist, not depending on the incubation time. This effect of carbachol was due to a reduction in the maximal binding capacity ($B_{max}$) to the mAchR without decreasing the affinity of the remaining receptors in incubation at 37.deg.C but was not apparent inincubation at $15^{\circ}}C$In addition, it was abolished when the receptors were blocked by atropine. The decline in ($^3H$)N-methylscopolamine (($^3H$)NMS) binding induced by agonist was reflected as a significant reduction in the receptor density with no change in receptor affinity, suggesting that 'true' receptor down-regulation takes place. Moreover, when the receptors were labeled with the lipophilic antagonist ($^3H$) quinuclidinyl benzilate (($^3H$) QNB) insted of the hydrophilic ligand ($^3H$)NMS, the magnitude of the observed receptor down-regulation was significantly lower in case of the former than the latter. This suggested that exposure of intact brain cells to muscarinic agonists might induce a slight degree of accumulation of receptors in intracellular sites before the receptors are actually degraded.

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Functional Characteristics of TRPC4 Channels Expressed in HEK 293 Cells

  • Sung, Tae Sik;Kim, Min Ji;Hong, Soojin;Jeon, Jae-Pyo;Kim, Byung Joo;Jeon, Ju-Hong;Kim, Seon Jeong;So, Insuk
    • Molecules and Cells
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    • 제27권2호
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    • pp.167-173
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    • 2009
  • The classical type of transient receptor potential (TRPC) channel is a molecular candidate for $Ca^{2+}$-permeable cation channels in mammalian cells. Because TRPC4 and TRPC5 belong to the same subfamily of TRPC, they have been assumed to have the same physiological properties. However, we found that TRPC4 had its own functional characteristics different from those of TRPC5. TRPC4 channels had no constitutive activity and were activated by muscarinic stimulation only when a muscarinic receptor was co-expressed with TRPC4 in human embryonic kidney (HEK) cells. Endogenous muscarinic receptor appeared not to interact with TRPC4. TPRC4 activation by $GTP{\gamma}S$ was not desensitized. TPRC4 activation by $GTP{\gamma}S$ was not inhibited by either Rho kinase inhibitor or MLCK inhibitor. TRPC4 was sensitive to external pH with $pK_a$ of 7.3. Finally, TPRC4 activation by $GTP{\gamma}S$ was inhibited by the calmodulin inhibitor W-7. We conclude that TRPC4 and TRPC5 have different properties and their own physiological roles.

Allyl Isothiocyanate 유발 피부염에 의한 척수후각세포의 활동성 변동 (Modification in the Responsiveness of Dorsal Horn Cells during Allyl Isothiocyanate-Induced Inflammation in the Cat)

  • 윤영복;김진혁;신홍기;김기순
    • The Korean Journal of Physiology
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    • 제24권2호
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    • pp.305-317
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    • 1990
  • The present study was performed to investigate modification in the electrophysiological characteristics of cat dorsal horn cells during neurogenic inflammation induced by mustard oil. The results obtained were summarized as follows: 1) Following subcutaneous injection of mustard oil the majority of wide dynamic range (WDR) cells (10/15 units) showed enhanced responses (80%) to brush, while the responses to all types of mechanical stiumli were enhanced in 3/15 units. One cell was further activated by pinch and the another was not affected at all after induction of inflammation. 2) The sensitization of WDR cell was resulted from subcutaneous injection of mustard oil either inside or outside of the receptive field (RF), whereas the spontaneous activity increased only after mustard oil was injected inside of the RF. 3) In the animal with inflammation the responses of high threshold (HT) cell to noxious stimulus were not altered, while HT cell responded to such mechanical stimulus as pressure which was usually ineffective in normal animals. 4) After induction of inflammation, low threshold (LT) cell appeared to be converted to WDR cell, showing responses not only to brush but also to pressure and pinch. 5) The mustard oil-induced inflammation enhanced responses of WDR and HT cells to the thermal stimuli and also resulted in a pronounced after-discharge in WDR cells. 6) After subcutaneous injection of lidocaine, the increased background activity of WDR cells due to inflammation was almost completely abolished. 7) A subcutaneous injection of mustard oil inside of the RF invariably desensitized the dorsal horn cells which receive sensory inputs from the inflamed RF. From the results of Present study it was revealed that a neurogenic inflammation induced by mustard oil resulted in an enhancement of responses of cat dorsal horn cells to mechanical and thermal stimuli.

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Proposal of a Selective Prophylaxis Strategy Based on Risk Factors to Prevent Early and Late Pneumocystis jirovecii Pneumonia after Renal Transplantation

  • Lee, Ho;Han, Ahram;Choi, Chanjoong;Ahn, Sanghyun;Min, Sang-il;Min, Seung-Kee;Lee, Hajeong;Kim, Yon Su;Yang, Jaeseok;Ha, Jongwon
    • 대한이식학회지
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    • 제32권4호
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    • pp.92-103
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    • 2018
  • Background: Currently, trimethoprim-sulfamethoxazole is used for Pneumocystis jirovecii pneumonia (PJP) prophylaxis, but it is associated with frequent adverse effects. This study evaluated the efficacy and safety of the current protocol and proposes an individualized risk-based prophylaxis protocol. Methods: The PJP incidence and risk factors during the first 6 months (early PJP) and afterwards (late PJP) was assessed in renal transplant recipients with (prophylaxis group) and without (no-prophylaxis group) 6-month PJP prophylaxis. Results: In 578 patients, there were 39 cases of PJP during a median follow-up of 51 months. Renal adverse events were encountered frequently during trimethoprim-sulfamethoxazole prophylaxis, leading to premature discontinuation. Patients without the prophylaxis had a significantly higher incidence of early PJP (n=27, 6.6%) compared to patients with the prophylaxis (n=0). The incidence of late PJP was 2.2%, without between-group differences. The factors associated with early PJP were preoperative desensitization and acute rejection within 1 month, whereas late PJP was associated with age, deceased donor transplant, and acute rejection requiring antithymocyte globulin treatment. Conclusions: Based on the simulation results of several risk-based scenarios, the authors recommend universal prophylaxis up to 6 months post-transplant and extended selective prophylaxis in patients aged ${\geq}57$ years and those with a transplant from deceased donors.

알루미늄 허니컴(HC) 구조재 적용 주조형 복합화약 (Structural Support of Aluminum Honeycomb on Cast PBX)

  • 김성한;이근득;박하늘;한민구
    • 한국군사과학기술학회지
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    • 제27권2호
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    • pp.222-229
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    • 2024
  • As the operating condition for the penetrating missile has been more advanced, the survivability of main charge has been strongly required when the warhead impacts the target. Lots of efforts to desensitize explosives such as the development of insensitive molecular explosives or optimizing plastic-bonded explosives(PBX) systems has been made to enhance the survivability of main charge. However, these efforts face their limits as the weapon system require higher performance. Herein, we suggest a new strategy to secure the survivability of main charge. We applied structurally supportable aluminum honeycomb(HC) structure to cast PBX. The aluminum HC structure reinforces the mechanical strength of cast PBX and helps it to withstand external pressure without the reaction like detonation. In this study, impact resistance character, shock sensitivity and internal blast performance of PBXs reinforced with HC structure were investigated according to the application of aluminum HC structure. The newly suggested aluminum HC structure applied to cast PBX was proved to be a promising manufacturing method available for high-tech weapon systems.

기관지 천식 환자에서 천식 증상의 정도에 따른 $\beta_2$ 교감신경 수용체의 유전자 다형성 (Genetic Polymorphisms of the $\beta_2$-Adrenergic Receptor in the Severity of Bronchial Asthma)

  • 심재정;김제형;이승룡;권영환;이소라;이상엽;강세용;강용구;조재연;인광호;원남희;유세화;강경호
    • Tuberculosis and Respiratory Diseases
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    • 제45권1호
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    • pp.77-89
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    • 1998
  • 서 론: $\beta_2$ 교감신경 수용체 유전자에는 여러 종류의 다형성(polymorphism)가 존재하며, 천식 환자에서 $\beta_2$ 교감신경 수용체의 대표적인 변이는 $\beta_2$ 교감신경 수용체의 아미노산이 대치된 부분으로 Arg16-Gly, Gln27-Glu, Val34-Met 및 Thr164-Ile 등인 것으로 알려져 있다. 지속적인 $\beta_2$ 교감신경 유도체의 자극에 대하여 세포표면으로 부터 세포내의 전달과정이 둔화되어 점차 세포전달이 없어질 수도 있는 desensitization 또는 수용체와 수가 감소하는 downregulation이 존재하는 것으로 알려져 있다. 천식환자에서 $\beta_2$ 교감신경 수용체의 desensitization 또는 downregulation 뿐만 아니라 천식 표현형과 $\beta_2$ 교감신경 수용체 유전자 다형성의 상관 관계에 대한 연구가 이루어지고 있으나 논란이 많다. 이에 본 연구는 기관지 천식환자에서 $\beta_2$ 교감신경 수용체의 가장 흔한 16, 27, 34 및 164 의 아미노산에 해당하는 유전자의 다형성을 MASA (Mutated Allele Specific Amplification)법으로 시행하여 각각의 다형성의 발생 빈도와 천식의 심한 정도와 연관이 있는 가를 확인하였다. 대상 및 방법: 대상 환자는 천식 환자 103명이었으며, 이중 남자는 54명, 여자는 49명으로 평균 연령은 46.6세 (19~80세)였고 이환 기간은 4.7년이었다. 대상 환자는 경미하고 간헐적 증상을 보인 30명, 지속적인 경미한 천식 환자는 32명으로 경미한 천식은 모두 62명이었으며, 중등증의 천식 증상은 17명 및 중종의 천식증상을 보인 환자는 24명이었다. 이중 1년 중에 6개월 이상 전신적 스테로이드를 투여하는 환자는 39명이었으며, 투약 중에도 야간 발작이나 야간 기침이 발생되었던 환자는 44명이었다. 대상 환자로부터 10cc의 전혈구를 체취 하여 분리된 림파구에서 분리된 DNA를 이용하여 MASA 방법으로 $\beta_2$ 교감신경 수용체 16번, 27번, 34번 및 164번째 아미노산의 다형성을 검색하였고, 천식의 심한 정도 따른 $\beta_2$ 교감신경 수용체 유전자의 다형성의 분포와 야간 천식의 발작이나 증상의 유무에 따른 $\beta_2$ 교감신경 수용체 유전자의 다형성의 분포를 확인하였다. 결 과: 16 번째 Arginine이 Glycine으로 변이는 heterozygous 변이가 67명, homozygous 변이가 13명으로 heterozygous 변이가 65.1%로 가장 많았다. 27번째 Glutamine이 Glutamate로 변이는 heterozygous만 11명으로 10.7%였으며, 34번째 Valine이 Methionine으로 변이를 일으키는 100번째 핵산의 경우도 heterozygous만 6명으로 5.8%였다. 27 번째와 34번째 아미노산의 변이를 일으키는 homozygous 변이와 164번째 아미노산의 변이는 대상 환자 중에는 없었다. 천식 증상의 심한 정도를 경종 및 중등증, 중중으로 2 구분하여 $\beta_2$ 교감신경 수용체 다형성의 발생빈도를 관찰한 결과 중증의 천식환자에서 16번째 아미노산의 변이의 빈도는 많았으나 (p=0.015), 27번, 34번 및 164번째의 아미노산의 변이는 천식 증상의 정도와는 연관성이 없었다. 야간 천식 증상의 유무에 따른 $\beta_2$ 교감신경 수용체 다형성은 16, 27, 34 및 164번째 아미노산의 핵산의 변이와 연관성이 없었다. 결 론: 이상의 결과로 기관지 천식 환자에서 $\beta_2$ 교감신경 수용체 다형성은 Arg 16, Gln 27 및 Val 34의 변이가 존재하고, Arg 16이 가장 많았으며, Thr 164는 없었다. 기관지 천식 환자에서 증상이 심한 중증 천식은 $\beta_2$ 교감 신경 수용체의 다형성중 Arg 16의 변이는 중증 천식과 연관성이 있었다. 그러나 야간 천식 발작이나 증상과 $\beta_2$ 교감신경 수용체 다형성은 서로 상관이 없었다.

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Dichlorvos가 흰쥐 심근의 미세구조에 미치는 영향 (A Study on the Ultrastructural Changes of Cardiac Muscle in Dichlorvos Treated Albino Rat)

  • 백태경;이화모;정호삼
    • Applied Microscopy
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    • 제24권3호
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    • pp.23-33
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    • 1994
  • It is well known that dichlorvos (DDVP), an organophosphate insecticide in common use, is so easily and rapidly hydrolyzed and excreted that it has usually little toxic effect on human body. In these days, however, it is widely used as an industrial and domestic insecticide and as an anthelmintic agent for animals, so that the accident of chemical poisoning occurs frequently. DDVP acts as a powerful inhibitor of carboxylic esterase, which can cause accumulation of acetylcholine at the synapses so paralysis of muscle and the transmission failure in cholinergic synapses dueing to desensitization of acetylcholin receptor may occure. Moreover accumulation of the acetylcholine brings about the elevation of the cyclic-AMP, which alters the cellular metabolisms of nucleic acid, carbohydrate, protein and lipid. Present study has undertaken to investigate the cardiotoxic effect of DDVP by electron microscopic study. A total of 30 Sprague-Dawley strain rats, weighing about 250gm were used as experimental animals. 2mg/kg/day of DDVP is intraperitonealy injected 3 times with intervals of every other day. On 1 day, 3 days, 5 days, 7 days and 14 days after drug administration, the animals were sacrified by cervical dislocation. Left ventricular cardiac muscles were resected and sliced into $1mm^3$. The specimens were embedded with Epon 812 and prepared by routine methods for electron microscopical observation. All preparations were stained with lead citrate and uranyl acetate and then observed with Hitachi-600 transmission electron microscope. The results were as follows: 1. In the cardiac muscle of DDVP treated rats, mitochondria with disorganized double membrane and mitochondrial crista, and vacuole formation in mitochondrial matrix were observed. But structures of mitochondria were recovered to normal in 14 days group. 2. In the cardiac muscle of DDVP treated rats, cisternae of sarcoplasmic reticulum were dilated and sacculated. But these changes were recovered to normal in 14 days group. 3. In the cardiac muscle of DDVP treated rats, glycogen particles around damaged myofibrils were decreased. But amount of glycogen particles were restored in 14 days group. 4. In the cardiac muscle of DDVP treated rats, disruption and discontinuation of myofilaments and disorganization of Z-disc were observed. But the structures of myofibrils were recovered to normal in 14 days group. It is consequently suggested that DDVP would induce the reversible degenerative changes on the ultrastructures in cardiac muscle of rat.

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