• 동의생리병리학회지
• /
• 제28권6호
• /
• pp.630-635
• /
• 2014

The purpose of this study was to investigate the effects of Naeso-san in interstitial cells of Cajal (ICCs) in murine small intestine. First, we isolated ICCs from murine small intestine. After that, we cultured these cells for 1 days. The patch-clamp technique was applied on ICCs that formed network-like structures in culture (1 days). Spontaneous rhythms were routinely recorded from cultured ICCs under current-clamp conditions, and the ICCs within networks displayed more robust electrical rhythms (pacemaker potentials). To understand the relationship between Naeso-san and pacemaker activity in ICCs, we examined the effects of Naeso-san on pacemaker potentials of ICCs. In current clamp mode (I = 0), the addition of Naeso-san (10 mg/ml - 50 mg/ml) decreased the amplitude and frequency of the pacemaker potentials of ICCs in a dose dependent manner. However, these effects were blocked by intracellular $GDP{\beta}S$, a G-protein inhibitor, and glibenclamide, a specific ATP-sensitive K+ channels blocker. Pretreatment with SQ-22536, an adenylate cyclase inhibitor, did not block the Naeso-san induced effects, whereas pretreatment with ODQ, a guanylate cyclase inhibitor, or L-NAME, an inhibitor of nitric oxide (NO) synthase blocked the Naeso-san induced effects. Our findings provide insight into unraveling the modulation of Naeso-san in pacemaker potentials of ICCs and developing therapeutic agents against gastrointestinal motility disorders.

• The Korean Journal of Physiology
• /
• 제28권1호
• /
• pp.37-50
• /
• 1994

Synthetic potassium channel openers (KCOs) are agents capable of opening K-channels in excitable cells. These agents are known to have their maximal potency in the smooth muscle tissue, especially in the vascular smooth muscle. Much attention has been focused on the type of K-channel that is responsible for mediating the effects of KCOs. As the KCO-induced changes are antagonized by glibenclamide, an $K_{ATP}$ (ATP-sensitive K-channel) blocker in the pancreatic ${\beta}-cell,\;K_{ATP}$ was suggested to be the channel responsible. However, there also are many results in favor of other types of K-channel $$(maxi-K,\;small\;conductance\;K_{Ca,}\; SK_{ATP}) mediating the effects of KCOs. Effects of lemakalim, (-)enantiomer of cromakalim (BRL 34915), on the spontaneous contractions and slow waves, were investigated in the antral circular muscle of the guinea-pig stomach. Membrane currents and the effects on membrane currents and single channel activities were also measured in single smooth muscle cells and excised membrane patches by using the patch clamp method. Lemakalim induced hyperpolarization and inhibited spontaneous contractions in a dose-dependent manner. These effects were blocked by glibenclamide and low concentrations of tetraethyl ammonium (< mM). Glibenclamide blocked the effect of lemakalim on the membrane potential and slow waves. The mechanoinhibitory effect of lemakalim was blocked by pretreatment with glibenclamide. In a whole ceIl patch clamp condition, lemakalim largely increased outward K currents. These outward K currents were blocked by TEA, glibenclamide and a high concentration of intracelIular EGTA (10 mM). Volatage-gated Ca currents were not affected by lemakalim. In inside-out patch clamp experiments, lemakalim increased the opening frequency of the large conductance $Ca^{2+}-activated$ K channels $(BK_{Ca},\;Maxi-K).$ From these results, it is suggested that lemakalim induces hyperpolarization by opening K-channels which are sensitive to internal Ca and such a hyperpolarization leads to the inhibition of the spontaneous contraction.

• Journal of Ginseng Research
• /
• 제39권4호
• /
• pp.314-321
• /
• 2015

Background: Ginseng belongs to the genus Panax. Its main active ingredients are the ginsenosides. Interstitial cells of Cajal (ICCs) are the pacemaker cells of the gastrointestinal (GI) tract. To understand the effects of ginsenoside Re (GRe) on GI motility, the authors investigated its effects on the pacemaker activity of ICCs of the murine small intestine. Methods: Interstitial cells of Cajal were dissociated from mouse small intestines by enzymatic digestion. The whole-cell patch clamp configuration was used to record pacemaker potentials in cultured ICCs. Changes in cyclic guanosine monophosphate (cGMP) content induced by GRe were investigated. Results: Ginsenoside Re ($20-40{\mu}M$) decreased the amplitude and frequency of ICC pacemaker activity in a concentration-dependent manner. This action was blocked by guanosine 50-[${\beta}-thio$]diphosphate [a guanosine-5'-triphosphate (GTP)-binding protein inhibitor] and by glibenclamide [an adenosine triphosphate (ATP)-sensitive $K^{+}$ channel blocker]. To study the GRe-induced signaling pathway in ICCs, the effects of 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (a guanylate cyclase inhibitor) and RP-8-CPT-cGMPS (a protein kinase G inhibitor) were examined. Both inhibitors blocked the inhibitory effect of GRe on ICC pacemaker activity. L-NG-nitroarginine methyl ester ($100{\mu}M$), which is a nonselective nitric oxide synthase (NOS) inhibitor, blocked the effects of GRe on ICC pacemaker activity and GRe-stimulated cGMP production in ICCs. Conclusion: In cultured murine ICCs, GRe inhibits the pacemaker activity of ICCs via the ATP-sensitive potassium ($K^{+}$) channel and the cGMP/NO-dependent pathway. Ginsenoside Re may be a basis for developing novel spasmolytic agents to prevent or alleviate GI motility dysfunction.

• 정신신체의학
• /
• 제3권2호
• /
• pp.166-173
• /
• 1995

저자는 녹내장환자의 정신과적 문제를 조사해 보고자 안과 외래에서 통원 치료중인 녹내장환자 38명의 불안과 우울정도를 STAI의 T-A와 BDI를 이용하여 측정, 37명의 정상 대조군과 비교하였으며, 성별, 연령, 학력, 종교, 결혼 상태에 따른 차이, 치료방법, 치료기간, 병합된 신체질환과의 관계들을 조사하여 다음과 같은 결과를 얻었다. 1) 연령, 학력, 종교, 결혼상태에 따른 불안 및 우울점수의 유의한 차이는 없었다. 2) 불안점수는 녹내장환자군과 정상 대조군사이에 유의한 차이가 없었으며 여자 환자의 불안이 정상 대조군에 비해 높은 경향을 보였다. 3) 녹내장환자는 정상 대조군에 비해 여자에서 우울점수가 유의하게 높았으며 (p < .01) 남자에서는 차이가 없었다. 4) 녹내장환자의 18.4%(남자환자의 10.5%, 여자환자의 26.4%)가 우울증으로 추정되며 28.9%(남자환자의 10.5%, 여자환자의 47.4%)가 우울한 경향을 보이고 있었다. 5) 베타 차단제 투여나 신체 질환의 유무, 또한 치료기간과 우울 증상의 유의한 상관관계는 없었다. 6) 녹내장환자에게 심리적 부담이 되는 요소로는 실명할 가능성에 대한 두려움, 매일 안약을 사용하거나 투약을 해야 하는 점 등이었다.

• 대한약리학회지
• /
• 제31권2호
• /
• pp.251-259
• /
• 1995

Pharmacokinetics and pharmacodynamics of metoprolol, a selective beta-l blocker, were examined for 360 minutes after intravenous bolus administration of metoprolol to 6 dogs. Plasma concentration and excreted amount in the urine metoprolol were measured by liquid chromatography with fluorescence detection. PR interval and heart rate were measured by ECG monitoring. Blood pressure was monitored through intraarterial catheter in femoral artery and cardiac output by thermodilution method using Swan-Ganz catheter. To analyze the effect site concentration-response relationship, plasma concentration and pharmacological effects were simultaneously fitted to a two pharmacokinetic compartment linked to pharmacodynamic model with NONLIN program. Results are as follows. 1) The plasma concentration of metoprolol after intrvenous injection decreased biexponentially. The terminal half-life estimated was $1.33{\pm}0.40$ hours and the volume of distribution at steady state (Vdss) and the total body clearance were $1.04{\pm}0.4\;L/kg,\;6.55{\pm}2.21\;L/hr$, respectively. The central compartment volume of distribution and peripheral compartment volume of distribution were $0.35{\pm}0.14L/kg\;and\;0.69{\pm}0.34L/kg$. The renal clearance and intercompartment clearance were $0.53{\pm}0.25\;L/min\;and\;0.35{\pm}0.19\;L/min$. 2) Simulated biophase concentration-response curve shows hyperbolic relationship and the estimated concentration-effect relationship was best explained by Emax model when the prolongation of PR interval and the reduction of the heart rate were used as pharmacodynamic parameters. Emax and EC50 were estimated to be $26.3{\pm}4.7\;msec\;and\;88.8{\pm}82.3\;g/ml$ for PR interval, and $48.7{\pm}18.8\;beats/min\;and\;113.5{\pm}78.7\;ng/ml$ for heart rate, respectively. 3) The changes of cardiac output-effect site concentration relationship was best fitted by a linear model and the slope of the relationship was $0.005{\pm}0.003$. Diastolic blood pressure-effect site concentration relationship was also explained by the linear model and the slope of the relationship was $0.038{\pm}0.034$.