• 융합정보논문지
• /
• 제10권10호
• /
• pp.109-114
• /
• 2020

이번 연구는 소화기계 출혈, 궤양 등에 대해 치료와 예방을 목적으로 사용되는 rebamipide에서 농도 의존적 장관 수축성 조절 기전에 대해 조사하고자 한다. 소화기 수축은 근육의 섬유의 조절에 의하여 일어난다. 실험용 쥐의 회장 과 결장을 적출하여 carbachol로 회장 과 결장의 근육수축을 유발하여 연구를 진행하였다. rebamipide 단독으로 장관수축을 억제하지 않고 소폭으로 carbachol 유도 수축을 높이는 것으로 관찰되었다. 소화기계 부작용을 일으키는 indomethacin 과 rebamipide를 흔히 병용하기에, 병용 효과를 관찰하였다. Indomethacin과 병용된 rebamipide는 장관 중 회장의 수축성을 증대시켰다. rebamipide는 장관중 회장에서 수축성을 증대시키고, NSAIDs에 의한 궤양에 대한 항궤양효과 외에 운동성도 일부 조절하는 것으로 생각된다.

• Journal of Acupuncture Research
• /
• 제27권3호
• /
• pp.117-126
• /
• 2010

Objectives : The purpose of this study was to compare the effect of needle retention(NR) and electro-acupuncture of low(EA(L)) and high(EA(H)) frequencies at Haegye($ST_{41}$) on intestinal hypermotility induced with carbachol in rats Methods : We made over-activated state of intestinal motility with carbachol in rats and caried out needle retention acupuncture, low frequency electro-acupuncture and high frequency electro-acupuncture at Haegye($ST_{41}$) or sham point in rat devided into pre-treatment group and post-treatment group. And we resulted as followings from measuring charcoal travel rate with observation of intestinal motility. Results : 1. None of acupuncture, low frequency electro-acupuncture and high frequency electro-acupuncture at $ST_{41}$ had significant influences on intestinal motility of rat in normal state. 2. Pre-treated with acupuncture, low frequency electro-acupuncture and high frequency electro-acupuncture and post-treated with acupuncture and low frequency electro-acupuncture at $ST_{41}$ didn't significantly influences intestinal motility in rat which over-activated with carbachol. 3. Post-treated with high frequency electro-acupuncture at $ST_{41}$ suppressed intestinal motility in rat which over-activated with carbachol. Conclusions : These results suggest that treatment high frequency electro-acupuncture at ST41 may be effective on gastric disorders such as intestinal hypermotility and its effect had more cure than prevention.

• Journal of Ginseng Research
• /
• 제12권2호
• /
• pp.135-144
• /
• 1988

갑상선호르몬 분비조절물질(TSH, DB cAMP, NaF, carbachol, isoproterenol, propranolol)과 인삼성분(total saponin, diol saponin, triol saponin)의 복합처리가 갑상선의 cAMP의 양에 미치는 영향을 알아보기 위하여, 흰쥐의 갑상선을 4일 또는 7일간 배양한 후 갑상선호르몬 분비조절물질과 인삼성분을 각각 복합처리, 또는 단독처리하여 cAMP의 양을 조사하였다. 인삼성분만을 처리한 경우, total saponin은 $10^{-5}$%(w/v), diol saponin과 triol saponin은 $10^{-4}$%(w/v)의 농도에서 각각 가장 높은 증가를 나타내었다. 갑상선호르몬 분비조절물질과 복합처리한 인삼성분의 농도는 위의 값으로 하였다. 복합처리한 경우, TSH에 대해서는 증가효과를 나타냈지만 그 양상은 작았다. Total saponin은 DBcAMP와 isoproterennol에 대해서는 증가효과를, carbachol과 propranolol에 대해서는 감소효과를 나타내었고, NaF에 대해서는 영향이 크지 않았다. Diol saponin과 triol saponin은 그 양은 다르지만 isoproterenol을 복합처리한 경우를 제외하고 diol saponin은 감소효과를, triol saponin은 증가효과를 보이는 상반작용을 나타내었다. 억제효과를 가지는 propranolol에 대해서도 diol saponin과 triol saponin은 상반되는 효과를 나타내었다. 인삼성분의 정상화작용은 NaF와 carbachol의 경우에도 두드러지게 나타났다. 이상의 결과들은 인삼성분이 갑상선호르몬의 생성과 분비에 관여하는 cAMP의 생성에 촉진 또는 억제를 가진다는 것을 나타내고 있다.

• The Korean Journal of Physiology and Pharmacology
• /
• 제4권2호
• /
• pp.105-111
• /
• 2000

Stimulation of muscarinic receptors by carbachol (CCh) in the circular smooth muscle of the guinea pig gastric antrum causes muscle contraction. In the present study, muscarinic receptor subtype controlling the muscle contraction in response to CCh was studied using putative muscarinic receptor antagonists. Isometric force of the isolated circular muscle strips was measured in an organ bath. CCh contracted the muscle in a dose-dependent way, and each of the three muscarinic receptor antagonists, 4-diphenylacetoxy- N-methylpeperdine methiodide (4-DAMP), methoctramine and pirenzepine shifted the concentration- response curves to the right without significantly reducing the maximum force. The affinities of the muscarinic antagonists $(pA_2\;values)$ obtained from Schild plot analysis were 10.15, 7.05 and 6.84 for 4-DAMP, methoctramine and pirenzepine, respectively. These results suggest that the $M_3-subtype$ mainly mediate the muscle contraction in response to CCh in guinea pig gastric antrum.

• 대한약리학회지
• /
• 제32권3호
• /
• pp.373-380
• /
• 1996

최근 본 연구실에서는 GS 386인 1-(4'-methoxybenzyl)-6,7-dimethoxy-3,4-dihydroisoquinoline이 적출된 토끼의 심방세포에서 $Ca^{++}$ 채널의 운동성 변화없이 $Ca^{++}$ 채널이 열릴 가능성을 줄임으로써 $Ca^{++}$ 전류의 증폭을 억제한다고 보고하였다. 이번 연구에서는 적출된 쥐의 기관지를 사용하여 GS 386의 작용기전에 대해 연구하였다. GS386은 carbachol $(0.3{\mu}M)$과 높은 농도의 $K^+$ (65.4mM)에 의해 수축된 쥐의 기관지를 용량-의존적으로 이완시켰으며 이때 $IC_{50}$는 5.24와 $5.67\;{\mu}M$이었다. verapamil은 carbachol에 의한 수축시 보다 높은 농도의 $K^+$에 의해 수축된 조직에 더욱 효과적으로 억제하였다. $Ca^{++}$이 없는 상태에서 $Ca^{++}$에 의한 수축은 GS386에 의해 억제되었다. 더욱이 높은 농도의 GS386$(100\;{\mu}M)$은 verapamil과는 다르게 carbachol뿐만 아니라 caffeine에 의한 위상성 수축을 억제 시키므로 GS386은 세포질내로 들어가 sarcoplasmic retuculum과 같은 근육 내부에 2차적인 영향을 나타내었다. 더군다나GS386은 verapamil에 의해 영향을 받지않는 (verapamil-insensitive component)이완을 보였고 쥐 기관지의 평활근에서 cAMP의 양을 증가 시켰다. 이러한 결과는 GS386의 작용기전이 $Ca^{++}$ 길항적인 작용 뿐만 아니라 posphodiesterase억제작용에 기인한다는 사실을 제시한다.

• Journal of Acupuncture Research
• /
• 제26권2호
• /
• pp.79-89
• /
• 2009

Objectives : The aim of this study was to observe the effect of acupuncture and high frequency electroacupuncture at $ST_{39}$ on intestinal motility in rats. Methods: We made over-activated state of intestinal motility with carbachol and suppressed state of intestinal motility with loperamide in rat and carried out needle retention acupuncture and high frequency electroacupuncture at $ST_{39}$ or sham point in rat divided into pre-treatment group and post-treatment group. We fed charcoal to them after the treatment and measured the travel rate of charcoal in the gastrointestinal tract to observe intestinal motility. Results : Examining intestinal motility of normal rat treated with needle retention acupuncture at $ST_{39}$ significantly suppressed intestinal motility. Pre-treatment of needle retention acupuncture significantly suppressed intestinal motility in rat which over-activated with carbachol. Pre-treatment and post-treatment of high frequency electroacupuncture significantly suppressed intestinal motility in rat which over-activated with carbachol. All of the pre-treatment and post-treatment of needle retention acupuncture, high frequency electroacupuncture showed no significant effect than control group on intestinal motility of rat which was suppressed with loperamide. Conclusions : These results suggest that acupuncture and high frequency electroacupuncture at $ST_{39}$ have preventive and therapeutic effects on over-activated intestinal motility, and high frequency electroacupuncture is more effective.

• Korean Journal of Acupuncture
• /
• 제25권2호
• /
• pp.179-197
• /
• 2008

Objectives and Methods : The purpose of this study was to observe the effects of acupuncture and electro-acupuncture (EA) at PC6 on intestinal motility in rats. We made over-activated state of intestinal motility with carbachol and suppressed state of intestinal motility with loperamide in rat, and carried out acupuncture with needle retained (NR), low frequency (2 Hz) EA and high frequency (100 Hz) EA at PC6 before or after the administration of carbachol or loperamide. The charcoal travel rate was measured to evaluate the intestinal motility. Results : 1. NR showed no significant influences on intestinal motility of rat in normal state. While, 2 Hz EA and 100 Hz EA at PC6 significantly increased the intestinal motility of rat in normal state. 2. All of the pre-treatment and post-treatment of NR, 2 Hz EA and 100 Hz EA at PC6 showed no significant effects on intestinal motility of rat which was over-activated with carbachol. 3. Both pre-treatment and post-treatment of NR significantly increased intestinal motility in rat which was suppressed with loperamide. 4. Pre-treatment of 2 Hz EA and post-treatment of 100 Hz EA significantly increased intestinal motility in rat which was suppressed with loperamide. Conclusions : These results suggest that acupuncture (NR) and EA on PC6 have preventive and therapeutic effect on suppressed intestinal motility, and NR may be more effective than EA in that condition.

• The Korean Journal of Physiology and Pharmacology
• /
• 제1권1호
• /
• pp.19-25
• /
• 1997

The C-terminus ends of the second putative transmembrane domains of both $M_1$ and $M_2$ muscarinic receptors contain a triplet of amino acid residues consisting of leucine (L), tyrosine (Y) and threonine (T). This triplet is repeated as LYT-TYL in $M_1$ receptors at the interface between the second transmembrane domain and the first extracellular loop. Interestingly, however, it is repeated in a transposedfashion (LYT-LYT) in the sequence of $M_2$ receptors. In our previous work, we investigated the possible significance of this unique sequence diversity for determining the distinct differential receptor function at the two receptor subtypes. However, we found mutation of the LYTTYL sequence of $M_1$ receptors to the corresponding $M_2$ receptor LYTLYT sequence demonstrated markedly enhanced the stimulation of phosphoinositide (PI) hydrolysis by carbachol without a change in its coupling to increased cyclic AMP formation. In this work, thus, the enhanced stimulation of PI hydrolysis in the LYTLYT $M_1$ receptor mutant was further investigated. The stimulation of PI hydrolysis by carbachol was enhanced in the mutant $M_1$ receptor, and this change was not due to alterations in the rate of receptor desensitization or sequestration. The observed larger response to carbachol at mutant $M_1$ receptors was also not due to an artifact resulting from selection of CHO cells which express higher levels of G-proteins or phospholipase C. Our data suggest that although the LYTTYL sequence in $M_1$ muscarinic receptors is not involved in determining receptor pharmacology, mutation of the sequence enhanced the coupling of $M_1$ receptors to the stimulation of phospholipase C.

• The Korean Journal of Physiology and Pharmacology
• /
• 제1권5호
• /
• pp.485-493
• /
• 1997

We investigated the effect of ${\alpha}-adrenergic$ and cholinergic receptor agonists on $Ca^{2+}$ current in adult rat trigeminal ganglion neurons using whole-cell patch clamp methods. The application of acetylcholine, carbachol, and oxotremorine ($50\;{\mu}M\;each$) produced a rapid and reversible reduction of the $Ca^{2+}$ current by $17{\pm}6%,\;19{\pm}3%,\;and\;18{\pm}4%$, respectively. Atropine, a muscarinic antagonist, blocked carbachol- induced $Ca^{2+}$ current inhibition to $3{\pm}1%$. Norepinephrine ($50\;{\mu}M$) reduced $Ca^{2+}$ current by $18{\pm}2%$, while clonidine ($50\;{\mu}M$), an ${\alpha}2-adrenergic$ receptor agonist, inhibited $Ca^{2+}$ current by only $4{\pm}1%$. Yohimbine, an ${\alpha}2-adrenergic$ receptor antagonist, did not block the inhibitory effect of norepinephrine on $Ca^{2+}$ current, whereas prazosin, an ${\alpha}1-adrenergic$ receptor antagonist, attenuated the inhibitory effect of norepinephrine on $Ca^{2+}$ current to $6{\pm}1%$. This pharmacology contrasts with ${\alpha}2-adrenergic$ receptor modulation of $Ca^{2+}$ channels in rat sympathetic neurons, which is sensitive to clonidine and blocked by yohimbine. Our data suggest that the modulation of voltage dependent $Ca^{2+}$ channel by norepinephrine is mediated via an α1-adrenergic receptor. Pretreatment with pertussis toxin (250 ng/ml) for 16 h greatly reduced norepinephrine- and carbachol-induced $Ca^{2+}$ current inhibition from $17{\pm}3%\;and\;18{\pm}3%\;to\;2{\pm}1%\;and\;2{\pm}1%$, respectively. These results demonstrate that norepinephrine, through an ${\alpha}1-adrenergic$ receptor, and carbachol, through a muscarinic receptor, inhibit $Ca^{2+}$ currents in adult rat trigeminal ganglion neurons via pertussis toxin sensitive GTP-binding proteins.

• Archives of Pharmacal Research
• /
• 제14권2호
• /
• pp.181-187
• /
• 1991

The muscarinic antagonist 1-[benzilic 4, 4'-$[^3H]$ QUINUCLIDINYL BENZILATE $([^3H]$ QNB) bound to a single class of muscarinic receptors with high affinity in rabbit ileal membranes. The $K_D\;and\;B_{ max}$ values for $([^3H]$ QNB calculated from analysis of saturation isotherms were 52.5 pM AND 154 fmol/mg, respectively. Chlopheniramine (CHP), histamine $H_1$ blocker, increased $K_D$ vlue for $([^3H]$QNB without affecting the binding site concentrations and Hill coefficient. The $K_i$ value of CHP for inhibition of $([^3H]$QNB binding in ileal membranes was 1.44\mu{M}$ and the pseudo-Hill coefficient for CHP was close to unit. In the functional assay carbachol, muscarinic agonist, increased the contractile force of ileum with $ED_{50}$ value of $0.11\mu{M}$. CHP caused the rightward shift of the dose-response curve to carbachol. The $pA_2$ value of CHP determined from Schild analysis of carbacholinduced contraction was 5.77 and the slope was unity indicating competitive antagonism with carbachol. The dissociation constant $(K_i)$ of CHP obtained in competitive experiments with $([^3H]$ QNB was similar to the $K_A$ value (1.69 \mu{M)}$ of CHP as inhibitor of carbachol induced contraction in rabbit ileum. This result suggest that the binding of $H_i$ blocker. CHP, vs $([^3H]$QNB to muscarinic receptors in ileal membranes represents an interaction with a receptor of physiological relevance.