• The Korean Journal of Physiology and Pharmacology
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• 제13권3호
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• pp.241-249
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• 2009

Although extracellular $Ca^{2+}$ entry through the voltage-dependent $Ca^{2+}$ channels plays an important role in the spontaneous phasic contractions of the pregnant rat myometrium, the role of the T-type $Ca^{2+}$ channels has yet to be fully identified. The aim of this study was to investigate the role of the T-type $Ca^{2+}$ channel in the spontaneous phasic contractions of the rat myometrium. Spontaneous phasic contractions and $[Ca^{2+}]_i$ were measured simultaneously in the longitudinal strips of female Sprague-Dawley rats late in their pregnancy (on day 18 ${\sim}$ 20 of gestation: term=22 days). The expression of T-type $Ca^{2+}$ channel mRNAs or protein levels was measured. Cumulative addition of low concentrations (< 1 ${\mu}M$) of nifedipine, a L-type $Ca^{2+}$ channel blocker, produced a decrease in the amplitude of the spontaneous $Ca^{2+}$ transients and contractions with no significant change in frequency. The mRNAs and proteins encoding two subunits (${\alpha}$ 1G, ${\alpha}$ 1H) of the T-type $Ca^{2+}$ channels were expressed in longitudinal muscle layer of rat myometrium. Cumulative addition of mibefradil, NNC 55-0396 or nickel induced a concentration-dependent inhibition of the amplitude and frequency of the spontaneous $Ca^{2+}$ transients and contractions. Mibefradil, NNC 55-0396 or nickel also attenuated the slope of rising phase of spontaneous $Ca^{2+}$ transients consistent with the reduction of the frequency. It is concluded that T-type $Ca^{2+}$ channels are expressed in the pregnant rat myometrium and may play a key role for the regulation of the frequency of spontaneous phasic contractions.

• Journal of Chest Surgery
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• 제32권4호
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• pp.404-407
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• 1999

식도의 혈종은 자발적이거나 손상후 이차적인 원인으로 발생하거나 드문 질환이다. 병인론은 논쟁에 여지가 있으나 환자의 응고 능력이나 혈종의 위치, 그리고 선행된 구토의 병력 등에 좌\ulcorner 된다. 정상적인 응고력이 있는 환자의 경우 구토와 Mallory-Weiss lesion 등이 식도 혈종을 형성하는데 일차적인 역할을 하는 것으로 알려져 있다. 이에 반해 비 정상적인 응고력을 가진 환자는 구토와 연관이 없고 60% 환자에서 하부 식도가 보존되고 여러부위에 혈종이 있는 경우가 많다. 증례에서는 환자가 구토를 자주하고 구역질을 자주하는 과거력을 가지고 있었고 B형 간염으로 인한 약간의 응고 장애가 있으면서 식도 근육에 분포하는 혈관의 손상으로 인한 식도근육내 혈종이 형성된 것으로 여겨지고 그로 인해 식도의 폐쇄증을 일으켜 연하곤란의 증상이 나타났다고 보여지고 수술소견으로는 하부 식도에 점막 층, 점막하층부위의 손상이 없이 안쪽의 환상(circular)근육과 바깥쪽의 경선(longitudinal)근육사이에 육아성조직이 포함된 혈종이 고여 있었다. 연세대학교 영동세브란스병원 흉부외과에서는 대증적인 요법에도 불구하고 증상의 호전없이 악화되는 식도 점막과 점막하층에 열상이 없이 발생한 1례의 원발성 식도근육내 혈종를 수술하여 성공적으로 시행하여 좋은 결과를 얻었기에 보고하는 바이다.

• The Korean Journal of Physiology and Pharmacology
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• 제18권5호
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• pp.383-390
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• 2014

Gastrointestinal motility consists of phasic slow-wave contractions and the migrating motor complex (MMC). Eupatilin (Stillen$^{(R)}$) has been widely used to treat gastritis and peptic ulcers, and various cytokines and neuropeptides are thought to be involved, which can affect gastrointestinal motility. We performed a study to identify the effects of eupatilin on lower gastrointestinal motility with electromechanical recordings of smooth muscles in the human ileum and colon. Ileum and colon samples were obtained from patients undergoing bowel resection. The tissues were immediately stored in oxygenated Krebs-Ringer's bicarbonate solution, and conventional microelectrode recordings from muscle cells and tension recordings from muscle strips and ileal or colonic segments were performed. Eupatilin was perfused into the tissue chamber, and changes in membrane potentials and contractions were measured. Hyperpolarization of resting membrane potential (RMP) was observed after administration of eupatilin. The amplitude, AUC, and frequency of tension recordings from circular and longitudinal smooth muscle strips and bowel segments of the ileum and colon were significantly decreased after admission of eupatilin. Eupatilin elicited dose-dependent decreases during segmental tension recordings. In conclusion, eupatilin (Stillen$^{(R)}$) showed inhibitory effects on the human ileum and colon. We propose that this drug may be useful for treating diseases that increase bowel motility, but further studies are necessary.

• The Korean Journal of Physiology and Pharmacology
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• 제1권6호
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• pp.797-808
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• 1997

Nitric oxide (NO) has been 3mown as a mediator of nonadrenergic, noncholinergic inhibitory neurotransmitter in intestinal smooth muscles. It has been suggested that NO donor such as sodium nitroprusside (SNP) produces relaxation of smooth muscle via activation of guanylate cyclase and elevation of cGMP levels. We have therefore investigated the effects of NO, using SNP, on muscle tension in the longitudinal smooth muscle of guinea-pig ileum. The possible role of cGMP was also investigated as well as the involvement of $K^+$ channel on SNP-induced inhibitory effect. The results are summarized as follows; high KCI-or CCh-activated contractions were inhibited by SNP in a concentration-dependent manner. 8-Br-cGMP also showed a similar effect in that of SNP TEA (1 mM) significantly reduced the SNP-induced inhibitory effect. SNP-induced effect was forther reduced by the presence of 10 mM TEA. On the other hand, 4-AP (0.1 mM), glibenclamide $(10\;{\mu}M)$ and apinain $(0.1\;{\mu}M)$ showed little effects on SNP-induced relaxation. Zaprinast significantly potentiated the SNP-induced inhibitory effect in all ranges. ODQ also significantly decreased the SNP-induced inhibitory effect. Pretreatment with CPA $(10\;{\mu}M)$ slightly reduced the SNP-induced inhibitory effect. From the above results, both effect mediated by NO and cGMP might be responsible for the activation of $Ca^{2+}$-activated $K^+$ channel by SNP in guinea-rig ileum. And this $K^+$ channel activation by SNP also contributes to the SNP-induced membrane hyperpolarization and relaxation.

• The Korean Journal of Physiology and Pharmacology
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• 제5권4호
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• pp.287-297
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• 2001

Contraction of smooth muscle is initiated by an increase in cytosolic $Ca^{2+}$ leading to activation of $Ca^{2+}$/ calmodulin-dependnet myosin light chain (MLC) kinase and phosphorylation of MLC. The types of contraction and signaling mechanisms mediating contraction differ depending on the region. The involvement of these different mechanisms varies depending on the source of $Ca^{2+}$ and the kinetic of $Ca^{2+}$ mobilization. $Ca^{2+}$ mobilizing agonists stimulate different phospholipases $(PLC-{\beta},\;PLD\;and\;PLA_2)$ to generate one or more $Ca^{2+}$ mobilizing messengers $(IP_3\;and\;AA),$ and diacylglycerol (DAG), an activator of protein kinase C (PKC). The relative contributions of $PLC-{\beta},\;PLA_2$ and PLD to generate second messengers vary greatly between cells and types of contraction. In smooth muscle cell derived form the circular muscle layer of the intestine, preferential hydrolysis of $PIP_2$ and generation of $IP_3$ and $IP_3-dependent\;Ca^{2+}$ release initiate the contraction. In smooth muscle cells derived from longitudinal muscle layer of the intestine, preferential hydrolysis of PC by PLA2, generation of AA and AA-mediated $Ca^{2+}$ influx, cADP ribose formation and $Ca^{2+}-induced\;Ca^{2+}$ release initiate the contraction. Sustained contraction, however, in both cell types is mediated by $Ca^{2+}-independent$ mechanism involving activation of $PKC-{\varepsilon}$ by DAG derived form PLD. A functional linkage between $G_{13},$ RhoA, ROCK, $PKC-{\varepsilon},$ CPI-17 and MLC phosphorylation in sustained contraction has been implicated. Contraction of normal esophageal circular muscle (ESO) in response to acetylcholine (ACh) is linked to $M_2$ muscarinic receptors activating at least three intracellular phospholipases, i.e. phosphatidylcholine-specific phospholipase C (PC-PLC), phospholipase D (PLD) and the high molecular weight (85 kDa) cytosolic phospholipase $A_2\;(cPLA_2)$ to induce phosphatidylcholine (PC) metabolism, production of diacylglycerol (DAG) and arachidonic acid (AA), resulting in activation of a protein kinase C (PKC)-dependent pathway. In contrast, lower esophageal sphincter (LES) contraction induced by maximally effective doses of ACh is mediated by muscarinic $M_3$ receptors, linked to pertussis toxin-insensitive GTP-binding proteins of the $G_{q/11}$ type. They activate phospholipase C, which hydrolyzes phosphatidylinositol bisphosphate $(PIP_2),$ producing inositol 1, 4, 5-trisphosphate $(IP_3)$ and DAG. $IP_3$ causes release of intracellular $Ca^{2+}$ and formation of a $Ca^{2+}$-calmodulin complex, resulting in activation of myosin light chain kinase and contraction through a calmodulin-dependent pathway.

• 대한약리학회지
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• 제24권1호
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• pp.103-109
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• 1988

Buxus microphylla var. koreana Nakai에 존재 하는 steroidal alkaloid인 cyclobuxine D는 흰쥐에 있어 심박동수 감소 작용, 적출 개구리 심장에서 수축력 감소작용, 토끼 적출 장관에서 acetylcholine과 $Ba^{++}$.에 유발되는 수축에 대한 억제작용 등을 나타낸다고 보고되었다. 본 연구에서는 흰쥐 적출 자궁에서 acetylcholine, oxytocin과 $Ba^{++}$에서 의해 나타나는 수축 작용에 대한 cyclobuxine D의 영향을 관찰하였으며, 또 흰쥐 적출장관에서 칼륨에 의해 활성화되는 칼슘채널에 대한 cyclobuxine D의 작용을 관찰하였다. Cyclobuxine D는 흰쥐 적출 자궁에서 acetylcholine, oxytocin과 $Ba^{++}$에 의해 증가되는 peak tension과 duration을 용량적으로 현저히 억제하였다. Cyclobuxine D는 oxytocin보다 acetylcholine에 의해 나타나는 수축작용에 대해 강하게 작용했다. 흰쥐 적출 장관(ileum)을 Ca을 고갈시킨 Tyrode's 용액에 $40{\sim}50$분 담그고 $Na^+$ 대신 $K^+$로 대체시킨 용액에 10분간 담근 후 1.8 mM $CaCl_2$를 가했을 때 이중적인 근육수축작용이 나타난다(Phasic and tonic increase in tension). Cyclobuxine D $(6.2{\times}10^{-5}\;M)$은 이 두 components를 유의하게 억제하였으며 tonic component가 최대치에 도달했을 때 cyclobuxine D $(3.1{\times}10^{-4}\;M)$을 가하면 근육은 긴장도를 빨리 상실했다. 이 결과는 적출 장관에 있어 칼륨에 의해 활성화되는 칼슘 채널이 cyclobuxine D에 의해 차단되고 있음을 나타낸다. 이상의 결과에서 cyclobuxine D의 흰쥐 적출 자궁에 대한 수축 억제 작용은 voltage-dependent calcium channel 차단에 밀접한 관련이 있는 것으로 사려된다.

• Applied Microscopy
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• 제28권3호
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• pp.363-377
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• 1998

After the investigation on the eye of Incilaria fruhstorieri with light and electron microscopes, the following results were obtained. The eye of Incilaria fruhstorferi comprises cornea, lens, vitreous body, retina, and optic nerve inward from the outside. Cornea is composed of squamous, cuboid, columnar and irregular cells, which appear to be light due to their low electron density. In their cytoplasms, glycogen granules, multivesicular body, and nucleus were observed. Vitreous body, located behind non-cellular transparent lens, is filled with long and short microvilli protruding from the retinal epithelia. Retinal epithelium, the organ to perceive objects, is divided into four parts; microvillar layer pigment layer, nuclear layer, and neutrophils layer, from the apical portion. Microvillar layer consists of the type-I photoreceptor cells and pigmented granule cells. In the apical portion of their cytoplasms, long microvilli (length, $19{\mu}m$) , short microvilli (length, $8{\mu}m$), and rolled microvilli grow thick in the irregular and mixed forms. Photoreceptor cells are classified into type-I and type-II, according to their structures. The type-I cell has the apical portion rising roundly like a fan and the lower part which looks like the helve of a fan. In the cytoplasm of the apical portion, there are clear vesicles, cored vesicles, ovoid mitochondria, and microfilaments, and in the cytoplasm of the lower part, photic vesicles with their diameters about 60nm aggregate densely. The type-II photoreceptor cell, located at the lower end of the type-I cells, has a very large ovoid nucleus 3nd no microvilli. In the cytoplasm of the type-II cell, the photic vesicles with sizes 60nm aggregate more densely than in the cytoplasm of the type-I cell. Pigmented cells are classified into type-A and type-B, according to their structures. The type-A is identified to be a large cell containing round granules (diameter, $0.5{\mu}m$) of very high electron density, while the type-B is identified as a small cell where the irregular granules (diameter, $0.6{\mu}m$) of a little lower electron density amalgamate. Nuclear layer ranges from the bottom of pigment layer to the top of the capsule, and contains three kinds of nuclei (nuclei of the type-II photoreceptor cell, pigmented granule cell, and accessory neuron). The capsules covering the outmost part of the eyeball are composed of collagenous fiber and three longitudinal muscle layers (the thickness of each longitudinal muscle layer, $0.4{\mu}m$) and thick circular muscle layer (thickness, $0.3{\mu}m$). Around the capsules, there is a neurophile layer consisting of neurons and nerve fibers. Each neuron has a relatively large ovoid nucleus for its cytoplasm, and in the karyosome, large lumps of keterochromatin form a wheel nucleus.

• 한국어류학회지
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• 제10권1호
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• pp.115-127
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• 1998

조피볼락의 소화관은 인두, 식도, 위, 장, 항문 그리고 10~11개의 유문수로 이루어져 있다. 유문수는 위의 유문부 말단에서 유래하며 바나나 형태의 맹낭을 형성하고 있다. 어체 체장에 대한 식도에서 항문까지의 소화관 길이의 비 (relative length of gut: RLG)는 1.56(n=10)이다. 식도의 근육층은 바깥쪽의 앓은 종주근층과 안쪽의 두꺼운 환상근층으로 구성된다. 점막상피층은 정단부에 짧은 미세융모를 가진 원주상피로 구성되며, 다수의 점액분비세포들을 가진다. 위의 점막주름은 규칙적으로 배열되었으며, 근육층은 종주근, 사주근, 환상근층으로 구성된다. 위선의 주세포는 관상의 미토콘드리아와 소포체 그리고 전자밀도가 높은 다수의 분비과립을 가지지만, 부세포는 소형의 미토콘드리아와 소포체 그리고 전자밀도가 낮은 액포를 가진다. 유문수와 장의 점막상피층은 주로 원주상피세포, rodlet cell 그리고 dark cell로 구성된다. 흡수기능을 가진 원주세포들은 발달된 미토콘드리아, 소포체, 전자밀도가 높은 과립상 물질, 음작용포 그리고 다포체를 가진다. Rodlet cell은 발달된 cytoplasmic capsule을 가지며 세포질에는 소포체가 잘 발달되어 있다. Dark cell의 세포질에는 전자밀도가 높고, 미토콘드리아들이 잘 발달되어 있다. 원주상피세포는 세포연접이 발달되어 있고, 상부에는 미세융모가 잘 발달되어 있으며, 미세융모의 내부에서는 세포질에서부터 시작된 actin filament를 관찰할 수 있다. 장 상피의 미세융모는 유문수의 미세융모 보다 길며, 배상세포의 수도 정상피에 더 많다.

• The Korean Journal of Physiology and Pharmacology
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• 제14권5호
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• pp.317-324
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• 2010

We elucidated the distribution of interstitial cells of Cajal (ICC) in human stomach, using cryosection and $c-Kit$ immunohistochemistry to identify $c-Kit$ positive ICC. Before $c-Kit$ staining, we routinely used hematoxylin and eosin (HE) staining to identify every structure of human stomach, from mucosa to longitudinal muscle. HE staining revealed that the fundus greater curvature (GC) had prominent oblique muscle layer, and $c-Kit$ immunostaining $c-Kit$ positive ICC cells were found to have typical morphology of dense fusiform cell body with multiple processes protruding from the central cell body. In particular, we could observe dense processes and ramifications of ICC in myenteric area and longitudinal muscle layer of corpus GC. Interestingly, $c-Kit$ positive ICC-like cells which had morphology very similar to ICC were found in gastric mucosa. We could not find any significant difference in the distribution of ICC between fundus and corpus, except for submucosa where the density of ICC was much higher in gastric fundus than corpus. Furthermore, there was no significant difference in the density of ICC between each area of fundus and corpus, except for muscularis mucosa. Finally, we also found similar distribution of ICC in normal and cancerous tissue obtained from a patient who underwent pancreotomy and gastrectomy. In conclusion, ICC was found ubiquitously in human stomach and the density of ICC was significantly lower in the muscularis mucosa of both fundus/corpus and higher in the submucosa of gastric fundus than corpus.

• The Korean Journal of Physiology
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• 제23권2호
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• pp.237-252
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• 1989

고양이 회장 종주근에서 세포막 소포를 분리하여 $Na^+$의 농도 경사에 의존하여 일어나는 $Ca^{2+}$ 이동의 특성에 대하여 연구하였다. 막소포 내부에서 외부로 향하는 $Na^+$의 농도 경사 존재시 $Ca^{2+}$의 축적이 현저히 증가하여 $Na^+$ 의존성 $Ca^{2+}$ 축적을 보였으며, 이는 외부용액에 $Na^+$ ionophore인 monensin을 처리시 소실되었다. 한편 이러한 $Ca^{2+}$ 축적의 증가 작용은 $Na^+$에 특이적이었으며 $K^+$, $Li^+$, $Rb^+$, $Cs^+$ 및 choline이온은 $Na^+$의 작용을 대치하지 못하였다. $Ba^{2+}$, $Sr^{2+}$, $Mn^{2+}$ 및 $Cd^{2+}$ 등의 2가 양이온들은 0.5 mM의 농도에서 $Na^+$ 의존성 $Ca^{2+}$ 축적을 억제하였으나 $Mg^{2+}$은 이 농도에서 억제 효과를 보이지 않았다. 막소포 외부의 pH를 pH 6.0에서 8.5까지 증가시 $Na^+$ 의존성 $Ca^{2+}$ 축적이 증가하였다. Amiloride는 0.5 mM 이상의 농도에서 $Na^+$ 의존성 $Ca^{2+}$ 축적을 유의하게 억제하였으나 diltiazem 및 vanadate는 이 농도에서 유의한 억제효과를 보이지 않았다. 동력학적으로 분석하여 측정한 $Na^+$ 의존성 $Ca^{2+}$ 축적의 $Ca^{2+}$에 대한 $K_m$ 값은 $18.2\;{\mu}M$이었으며 5초에서 측정한 $V_{max}$값은 689.7 pmole/mg protein이었다. $Ca^{2+}$ 축적에 대한 $Na^+$ 농도 경사의 효과를 동력학적으로 분석한 결과 막소포 외부에서의 $Ca^{2+}$에 대한 친화도에는 변화없이 최고 이동치만 증가시켜 전형적인 비상경적 작용 양상을 보였다. $Ca^{2+}$ 축적에 대한 $Na^+$ 농도 경사의 효과를 $Na^+$ 농도에 따라 측정하여 Hill plot을 시행한 결과 Hill coefficient가 2.52로 나타났다. 막소포 내부로 향하는 $K^+$ 농도 경사하에서 valinomycin을 처리하여 막소포 내부에 양전위를 발생시킨 결과 $Na^+$ 의존성 $Ca^{2+}$ 축적이 증가하였다. 이와 같은 결과들은 고양이 회장 평활근에서 분리한 세포막에 $Na^{+}-Ca^{2+}$ 교환기전이 존재하고 이는 다른 조직에서 밝혀진 것과 유사한 특성을 지녔으며 electrogenic한 기전으로 작용할 가능성을 시사하였다.