고양이 담낭 평활근에서 Cholecystokinin 및 Acetylcholine 유도 수축에 있어서 Calcium 이용 및 세포내 전달 기전에 대한 연구

이언탁,임병용,이원석 부산의대 1991 부산의대잡지 - 부산대학교 의과대학 Vol.31 No.2

위절제술 후 Carboxy-Methylcellulose를 이용한 위장관 조영술

오재천,김용수,문원진,임현철,고병희,조온구 한양대학교 의과대학 1997 한양의대 학술지 Vol.17 No.1

The purpose of this study was to determine the usefluness of the UGI study with Carboxy-Methylcellulose (CMC) and 140% barium in the patient undergone gastrectomy We reviewed the UGI study with effervescent agent and barium and the UGI study with CMC and 140% barium of twenty one patients, undergone gastrectomy (Billroth-Ⅱ:12, Billroth-Ⅰ:4 total gastrectomy:5). The average interval between these studies was 19 months. The coating quality of the remnant stomach, anastomosis sit e, jejunum and proximal ileum in two studies were compared. The maximum luminal diameter of the same site and the maximum distance between a adjacent valvulae conniventes were measured for evaluating the distensibility of these studies. Compared with the coating quality of the remnant stomach, the UGI study with effervescent agent and barium was superior to the UGI study with C MC and barium in 68% (11/16) patients. The difference of coating quality between these studies was marginal in the anastomosis site and jejunum. The UGI study with CMC and barium provided a better coating quality in the proximal ileum of 95%(20/21). The maximum luminal diameter of the anastomosis site, jejunum and proximal ileum was respectively 2.75cm, 3.36cm, and 2.82cm inthe UGI study with effervescent agent and barium, 3.2cm 3.35cm, and 3.40cm in the UGI study with CMC and barium(p〈0.01). The maximum distance between a adjacent valvulae conniventes of the jejunum and proximal ileum was respectively 0.61cm and 0.51cm in the UGI study with effervesent agent and barium, 0.74cm and 0.72cm in the UBI study with CMC and barium (p〈0.05). Compared with the distensibility, the UGI study with CMC and barium was superior. The UGI study with CMC and barium in subjects, undergone gastectomy, showed the advantage the mucosa distal to anastomosis site except for the remnant stomach and must be supply the more information in finding lesion such as adhesion and peritoneal dissemination.

Vascular Smooth Muscle Cells Secrete CXCL10 in Response to Heat Shock Protein 90

Byung-Yong Rhim(임병용),Do-Hyung Kim(김도형),Koanhoi Kim(김관회) 한국생명과학회 2011 생명과학회지 Vol.21 No.5

Heat shock protein (HSP)은 외부적인 자극에 반응하여 세포를 보호하는 역할을 한다. 또한 HSP90은 혈관질환에서 처럼 세포가 사멸되거나 손상을 입는 경우 세포 밖으로 유리된다. 그러나 지금까지 세포 밖 HSP90이 혈관 평활근세포에 어떠한 영향을 주는지에 대한 연구는 미약하다. 따라서 본 연구는 혈관평활근세포에서 HSP90이 CXCL10 발현에 대한 영향과 그 기전을 규명하였다. HSP90에 노출된 혈관평활근세포에서 CXCL10 transcript가 증가하고, CXCL10 단백질의 분비가 증가되었다. HSP90에 의한 CXCL10 분비는 Toll-like receptor (TLR)-2/-4 억제제인 1-palmitoyl-2-arachidonosyl-sn-phosphatidylcholine (OxPAPC)과 NADPH oxidase 억제제인 diphenyleneiodium 그리고 Akt 경로를 억제하는 LY294002와 Akti Ⅳ에 의하여 크게 감소되었다. 또한 TLR-4의 dimerization을 저해하는 curcumin 역시 HSP90에 의한 CXCL10의 분비를 억제하였다. 전사인자인 nuclear factor kappa B(NF-κB)의 생물학적 억제제인 inhibitory kappa B (IκB)와 NF-κB 억제작용이 있는 rasveratrol은 HSP90에 의한 CXCL10 분비를 억제하였다. 이러한 결과는 혈관평활근세포에서 HSP90에 의한 CXCL10의 발현에 TLR-4와 Akt 및 NF-κB가 관여함을 의미한다. Oxidative stress results in sustained release of heat shock protein 90 (HSP90) from vascular smooth muscle cells (VSMCs). We investigated whether extracellular HSP90 predisposed VSMCs to pro-inflammatory phenotype. Exposure of human aortic smooth muscle cells to HSP90 not only significantly enhanced CXCL10 secretion but also increased CXCL10 transcription. HSP90-mediated CXCL10 secretion was attenuated by OxPAPC, a TLR-2/4 inhibitor, and curcumin, a TLR-4 dimerization inhibitor. Inhibitors of diphenyleneiodium chloride and the Akt pathway also attenuated CXCL10 secretion in response to HSP90. The gene delivery of IκB using recombinant adenoviruses and treatment with resveratrol, which inhibit NF-κB activity, significantly attenuated HSP90-induced CXCL10 secretion from VSMCs. We propose that extracellular HSP90 contributes to an inflammatory reaction in the stressed vasculature by inducing CXCL10 expression of VSMCs, and that TLR-4, Akt, and NF-κB play active roles in the process.

Roles of TLR-4 and NF-κB in Interleukin-6 Expression Induced by Heat Shock Protein 90 in Vascular Smooth Muscle Cells

Byung-Yong Rhim(임병용),Kang-Seong Kim(김강성),Koanhoi Kim(김관회) 한국생명과학회 2008 생명과학회지 Vol.18 No.12

HSP90에 노출된 혈관평활근세포에서 IL-6 transcript가 증가하고, IL-6 단백질의 분비가 증가하며, 또한 IL-6 유전자의 promote가 활성화되었다. HSP90에 의한 IL-6 유전자의 promoter 활성화는 dominant negative 형태의 TLR-4와 MyD88에 의하여 크게 감소되었지만, dominant negative 형태의 TLR-3와 TRIF의 영향을 받지 않았다. 그리고 TLR-4의 이합체화(dimerization)를 저해하는 curcumin은 HSP90에 의한 IL-6의 분비 및 IL-6 유전자 promoter 활성화를 억제하였다. 그리고 IL-6 유전자의 promoter의 NF-κB- 또는 C/EBP-binding sequence에 변이는 HSP90에 의한 IL-6 유전자의 promoter 활성화 억제하였다. 이러한 결과는 혈관평활근세포에서 HSP90에 의한 IL-6 유전자 활성화에 TLR-4와 NF-κB가 관여함을 의미한다. This study has investigated whether extracellular HSP90 predisposes vascular smooth muscle cells (VSMCs) to pro-inflammatory phenotype. Exposure of rat aortic smooth muscle cells to HSP90 not only enhanced IL-6 release but also profoundly induced IL-6 transcript via promoter activation. HSP90-induced IL-6 promoter activation was suppressed by dominant-negative forms of Toll-like receptor (TLR)-4 and myeloid differentiation factor 88 (MyD88), but not by dominant-negative-forms of TLR-3 and TIR-domain-containing adapter-inducing interferon-β (TRIF). Curcumin, which inhibits dimerization of TLR-4, also attenuated the IL-6 induction by HSP90. Mutation at the NF-κB- or C/EBP-binding site in the IL-6 promoter region suppressed the promoter activation in response to HSP90. The gene delivery of IκB using recombinant adenoviruses and treatment with resveratrol, which inhibit NF-κB activity, attenuated the HSP90-induced IL-6 release from VSMCs. The present study proposes that extracellular HSP90 would contribute to inflammatory reaction in the stressed vasculature by inducing IL-6 in VSMCs, and that TLR-4 and NF-κB would play active roles in the process.

Pharmacological Evidence that Cromakalim Inhibits $Ca^{2+}$ Release from Intracellular Stores in Porcine Coronary Artery

Rhim, Byung-Yong,Hong, Sun-Hwa,Kim, Chi-Dae,Lee, Won-Suk,Hong, Ki-Whan The Korean Society of Pharmacology 1997 The Korean Journal of Physiology & Pharmacology Vol.1 No.1

In the present study, it was aimed to further indentify the intracellular action mechansm of cromakalim and levcromakalim in the porcine coronary artery. In intact porcine coronary arterial strips loaded with fura-2/AM, acetylcholine caused an increase in intracellular free $Ca^{2+}$ $([Ca^{2+}]_i)$ in association with a contraction in a concentration-dependent manner. Cromakalim (1 ${\mu}M$) caused a reduction in acetylcholine-induced increased $[Ca^{2+}]_i$ not only in the mormal physiological salt solution (PSS) but also in $Ca^{2+}$-free PSS (containing 1 mM EGTA). In the skinned strips prepared by exposure of tissue to 20 .${\mu}M$ B-escin, inositol 1,4,5-trisphosphate ($IP_3$) evoked an increase in $[Ca^{2+}]_i$, but it was without effect on the intact strips. The $IP_3$-induced increase in $[Ca^{2+}]_i$ was inhibited by cromakalim by 78% and levcromakalim by 59% (1 .${\mu}M$, each). Pretreatment with glibenclamide (a blocker of ATP-sensitive $K^+$ channels, 10 .${\mu}M$) and apamin (a blocker of small conductance $Ca^{2+}$-activated $K^+$ channels, 1 .${\mu}M$) strongly blocked the effect of cromakalim and levcromakalim. However, charybdotoxin (a blocker of large conductance $Ca^{2+}$-activated $K^+$ channels, 1 .${\mu}M$) was without effect. In addition, cromakalim inhibited the $GTP{\gamma}S$ (100 .${\mu}M$, non-hydrolysable analogue of GTP)-induced increase in $[Ca^{2+}]_i$. Based on these results, it is suggested that cromakalim and levcromakalim exert a potent vasorelaxation, in part, by acting on the $K^+$ channels of the intracellular sites (e.g., sarcoplasmic reticulum membrane), thereby, resulting in decrease in release of $Ca^{2+}$ from the intracellular storage site.

Cellular Pathways in Agonist-induced Gallbladder Muscle Contraction in the Cat

Rhim, Byung-Yong,Kim, Chi-Dae,Kim, Dong-Heon,Biancani, Piero,Behar, Jose The Korean Society of Pharmacology 1996 대한약리학잡지 Vol.32 No.1

고양이 담낭근에서 효소학적으로 분리한 평활근 세포는 cholecystokinin octapeptide (CCK-8), acetylcholine (ACh) 및 KCl에 의하여 용량에 의존하여 수축하였다. 이들 효현제 (CCK-5, ACh 및 KCl)에 의한 평활근 세포의 최대수축은 각각$10^{-9}M$, $10^{-5}M$ 및 20mM 농도에서 야기되었다. CCK-8에 의하여 야기되는 이들 평활근 세포의 수축은 HEPES 완충액에 $Ca^{2+}$을 제거시킴에 의하여 영향을 받지 아니하였으나, $Ca^{2+}$ 대신에 strontium을 첨가시켰을때 수축반응이 완전하게 억제되었다 (p<0.001). 이와는 반대로 KCl에 의한 수축반응은 strontium 치환에 의하여 영향을 받지 아니하고 HEPES 완충액에 $Ca^{2+}$을 제거시킴에 의하여 억제되었다 (p<0.01). ACh에 의하여 야기되는 수축반응은 세포 외액의 $Ca^{2+}$을 제거시킴에 의하여 중등도의 억제반응이 야기되었으나 (p<0.05) strontium에 의하여 영향을 받지 아니하였다. Saponin으로 세포 투과성 변동을 야기시킨 근세포에서 inositol 1,4,5-trisphosphate $(IP_3)$와 CCK-8은 수축반응을 일으켰고, 이러한 수축반응은 calmodulin 길항제인 CGS 9343B에 의하여 차단되었으며 (p<0.001), heparin은 CCK-8 및 $IP_3$의 작용을 완전하게 봉쇄하였다 (p<0.001). 그러나 이러한 수축반응에 있어서 protein kinase C 길항제인 H7은 아무런 작용을 나타내지 못하였다. 이러한 결과로 볼 때 CCK-8에 의하여 야기된 고양이 담낭근 세포의 수축반응은 $IP_3$에 의하여 세포내 저장소로부터 유리된 $Ca^{2+}$과 calmodulin에 의존적인 과정에 의하여 매개되어 지는 것으로 생각된다. 또한 ACh는 세포외액의 $Ca^{2+}$ 뿐만 아니라 세포내 저장소의 $Ca^{2+}$ 모두를 이용하며, KCl은 전적으로 세포외액의 $Ca^{2+}$에 의존적인 형태로 calmodulin과는 무관하게 고양이 담낭근 세포의 수축반응을 야기시키는 것으로 사료된다. Cholecystokinin octapeptide (CCK-8), acetylcholine (ACh) and KCl caused a dose dependent contraction in muscle cells enzymatically digested from cat gallbladder. Maximal contraction was obtained at concentration of $10^{-9}M$ for CCK-8, $10^{-5}M$ for ACh and 20mM for KCl. CCK-8 induced contraction was unaffected in calcium free physiological salt solution (PSS) and was completely blocked by strontium substitution for calcium (p<0.001). In contrast, KCl evoked contraction was blocked in calcium free PSS (p<0.01) but was unaffected by strontium replacement of calcium. The contraction elicited by ACh was only slightly reduced in calcium free PSS (p<0.05) and was unaltered by strontium. Muscle cells permeabilized with saponin contracted in response to inositol 1,4.5-trisphosphate $(IP_3)$ and CCK-8. The contraction was blocked by the calmodulin antagonist CGS 9343B (p<0.001), whereas heparin completely blocked the effect of $IP_3$ (p<0.001). The protein kinase C (PKC) antagonist H7 had no effect on either agonist. We conclude that CCK-8 induced gallbladder muscle contraction is mediated by $IP_3$ dependent intracellular calcium release from intracellular stores and a calmodulin dependent pathway; ACh may utilize both extracellular and intracellular calcium. KCl causes muscle contracrion through influx of extracellular calcium and a calmodulin independent machanism.

Pharmacological Evidence that Cromakalim Inhibits Ca<SUP>2⁢</SUP> Release from Intracellular Stores in Porcine Coronary Artery

Byung Yong Rhim,Sun Hwa Hong,Chi Dae Kim,Won Suk Lee,Ki Whan Hong 대한생리학회-대한약리학회 1997 The Korean Journal of Physiology & Pharmacology Vol.1 No.1

<P> In the present study, it was aimed to further indentify the intracellular action mechansm of cromakalim and levcromakalim in the porcine coronary artery. In intact porcine coronary arterial strips loaded with fura-2/AM, acetylcholine caused an increase in intracellular free Ca<SUP>2⁢</SUP> ([Ca<SUP>2⁢</SUP>]<SUB>i</SUB>) in association with a contraction in a concentration-dependent manner. Cromakalim (1 ㄍM) caused a reduction in acetylcholine-induced increased [Ca<SUP>2⁢</SUP>]<SUB>i</SUB> not only in the mormal physiological salt solution (PSS) but also in Ca<SUP>2⁢</SUP>-free PSS (containing 1 mM EGTA). In the skinned strips prepared by exposure of tissue to 20 ㄍM ㄂-escin, inositol 1,4,5-trisphosphate (IP<SUB>3</SUB>) evoked an increase in [Ca<SUP>2⁢</SUP>]<SUB>i</SUB>, but it was without effect on the intact strips. The IP<SUB>3</SUB>-induced increase in [Ca<SUP>2⁢</SUP>]<SUB>i</SUB> was inhibited by cromakalim by 78% and levcromakalim by 59% (1 ㄍM, each). Pretreatment with glibenclamide (a blocker of ATP-sensitive K<SUP>⁢</SUP> channels, 10 ㄍM) and apamin (a blocker of small conductance Ca<SUP>2⁢</SUP>-activated K<SUP>⁢</SUP> channels, 1 ㄍM) strongly blocked the effect of cromakalim and levcromakalim. However, charybdotoxin (a blocker of large conductance Ca<SUP>2⁢</SUP>-activated K<SUP>⁢</SUP> channels, 1 ㄍM) was without effect. In addition, cromakalim inhibited the GTP<SUB>㄃</SUB>S (100 ㄍM, nonhydrolysable analogue of GTP)-induced increase in [Ca<SUP>2⁢</SUP>]<SUB>i</SUB>. <P> Based on these results, it is suggested that cromakalim and levcromakalim exert a potent vasorelaxation, in part, by acting on the K<SUP>⁢</SUP> channels of the intracellular sites (e.g., sarcoplasmic reticulum membrane), thereby, resulting in decrease in release of Ca<SUP>2⁢</SUP> from the intracellular storage site.

흰쥐의 뇌 기저동맥에서 CGRP에 의한 혈관 이완반응의 기전에 대한 연구

임병용(Byung Yong Rhim),홍선화(Sun Hwa Hong),김치대(Chi Dae Kim),이원석(Won Suk Lee),김동헌(Dong Heon Kim),홍기환(Ki Whan Hong) 대한약리학회 1996 대한약리학잡지 Vol.32 No.1

본 실험에서는 흰쥐의 뇌 기저동맥을 이용하여 K⁺과 U46619에 의한 수축과 세포내 Ca²⁺의 변동을 관찰하고, 이들 반응을 CGRP 전처치시 나타나는 반응과 비교하였다. CGRP (30과 100 nM)는 U46619에 의하여 야기된 수축반응과 세포내 Ca²⁺의 증가반응을 억제시켰으나, K⁺ (90 mM)에 의하여 나타나는 반응에는 영향을 미치지 아니하였다. 게다가, U46619에 의하여 야기되는 장력에 대하여 세포내 Ca²⁺의 변동 (F₃₄₀/F₃₈₀)을 도표화하여 세포내 Ca²⁺ 농도와 장력의 발생과의 상관관계를 검토하고, 이들 결과를 CGRP 전처치시 나타나는 결과와 비교하였다. CGRP (30과 100 nM) 전처치군에서 얻어진 직선이 오른쪽으로 치우치지는 않으면서 아래쪽으로 이동하는 점으로 볼 때, CGRP가 Ca²⁺에 대한 수축기구의 감수성에는 영향을 미치지 않으면서 세포내 Ca²⁺ 농도를 저하시킴에 의하여 U46619에 의한 근수축반응을 억제시키는 것으로 보여진다. 이러한 CGRP의 효과는 CGRP1 수용체 길항제인 CGRP(8 ~ 37) 분획(100 nM)의 전처치시 현저히 억제되었다. CGRP에 의한 수축력과 세포내 Ca²⁺의 저하는 large conductance Ca²⁺에 의하여 활성화되는 K⁺ 통로 봉쇄제인 charybdotoxin (100 nM)과 iberiotoxin (100 nM)의 전처치에 의하여 완전하게 역전되었으나, small conductance Ca²⁺에 의하여 활성화되는 K⁺ 통로 봉쇄제인 apamin (300 nM)과 ATP에 감수성이 높은 K⁺ 통로 봉쇄제인 glibenclamide (1 μM)에 의해서는 영향을 받지 아니하였다. 이상의 결과로 볼 때 CGRP1 수용체는 Ca²⁺에 의하여 활성화되는 K⁺ 통로를 개방시킴으로 세포내 Ca²⁺을 감소시켜 뇌 기저동맥의 이완반응을 매개하는 것으로 사료된다. In the present study, we observed change in intracellular Ca²⁺([Ca²⁺]_i) as measured with the fluorescent Ca²⁺-indicator fura-2 in association with force development of the rat basilar arteries during activation byK⁺ depolarizing solution and U46619, a thromboxane analogue, in the absence and the presence of calcitonin-gent related peptide (CGRP). CGRP (30 and 100 nM) caused a concentration-dependent inhibition of U46619-induced contraction with decrease in [Ca²⁺]_i, whereas it did not exert any effect on the K⁺ (90 mM)-induced contraction and increase in [Ca²⁺]_i, Further, [Ca²⁺]_i-force relationships were determined by plotting the ratio of F₃₄₀/F₃₈₀ ([Ca²⁺]_i) as a function of the force induced by U46619, and the results were compared with those obtained in the presence of CGRP. The curves obtained in the presence of CGRP (30 and 100 nM) were significantly moved to downward without right shift of the curves suggesting that CGRP inhibited the U46619-induced contraction only by mediation of reduction in [Ca²⁺]_i with out any change in the sensitivity of contractile apparatus to Ca²⁺. The CGRP-induced attenuation of [Ca²⁺]_i and force development was significantly inhibited under pretreatment with CGRP (8 ~ 37) fragment (100 nM), a CGRP1 receptor antagonist. Both the reduced contraction and reduction in [Ca²⁺]_i caused by CGRP were fully reversed by pretreatment with charybdotoxin (100 nM) and iberiotoxin (100 nM), large conductance Ca²⁺-activated K⁺ channel blockers, but not by apamin (300 nM), a small conductance Ca²⁺-activated K⁺ channel blocker, and glibenclamide ( 1 μM), an ATP-sensitive K⁺ channel blocker. In conclusion, it is suggested that the CGRP1 receptor, upon activation by CGRP, are coupled to opening of Ca²⁺-activated K⁺ channel and cause to decrease in [Ca²⁺]_i, thereby leading to vasodilation of the rat basilar artery. However, it is not defined that the mechanism underlying vasodilation whether the K⁺ channel blockers, charybdotoxin and iberiotoxin directly block the CGRP receptors and that CGRP-evoked relaxation is dependent on the cyclic AMP or K⁺ channel opening or both actions.

고양이의 담낭근 수축에 있어서 세포내 기전

임병용(Byung Yong Rhim),김치대(Chi Dae Kim),김동헌(Dong Heon Kim),Piero Biancani,Jose Behar 대한약리학회 1996 대한약리학잡지 Vol.32 No.1

고양이 담낭근에서 효소학적으로 분리한 평활근 세포는 cholecystokinin octapeptide (CCK-8), acetylcholine (ACh) 및 KCl에 의하여 용량에 의존하여 수축하였다. 이들 효현제 (CCK-5, ACh 및 KCl)에 의한 평활근 세포의 최대수축은 각각10^-9M, 10^-5M 및 20mM 농도에서 야기되었다. CCK-8에 의하여 야기되는 이들 평활근 세포의 수축은 HEPES 완충액에 Ca²⁺을 제거시킴에 의하여 영향을 받지 아니하였으나, Ca²⁺ 대신에 strontium을 첨가시켰을때 수축반응이 완전하게 억제되었다 (p<0.001). 이와는 반대로 KCl에 의한 수축반응은 strontium 치환에 의하여 영향을 받지 아니하고 HEPES 완충액에 Ca²⁺을 제거시킴에 의하여 억제되었다 (p<0.01). ACh에 의하여 야기되는 수축반응은 세포 외액의 Ca²⁺을 제거시킴에 의하여 중등도의 억제반응이 야기되었으나 (p<0.05) strontium에 의하여 영향을 받지 아니하였다. Saponin으로 세포 투과성 변동을 야기시킨 근세포에서 inositol 1,4,5-trisphosphate (IP₃)와 CCK-8은 수축반응을 일으켰고, 이러한 수축반응은 calmodulin 길항제인 CGS 9343B에 의하여 차단되었으며 (p<0.001), heparin은 CCK-8 및 IP₃의 작용을 완전하게 봉쇄하였다 (p<0.001). 그러나 이러한 수축반응에 있어서 protein kinase C 길항제인 H7은 아무런 작용을 나타내지 못하였다. 이러한 결과로 볼 때 CCK-8에 의하여 야기된 고양이 담낭근 세포의 수축반응은 IP₃에 의하여 세포내 저장소로부터 유리된 Ca²⁺과 calmodulin에 의존적인 과정에 의하여 매개되어 지는 것으로 생각된다. 또한 ACh는 세포외액의 Ca²⁺ 뿐만 아니라 세포내 저장소의 Ca²⁺ 모두를 이용하며, KCl은 전적으로 세포외액의 Ca²⁺에 의존적인 형태로 calmodulin과는 무관하게 고양이 담낭근 세포의 수축반응을 야기시키는 것으로 사료된다. Cholecystokinin octapeptide (CCK-8), acetylcholine (ACh) and KCl caused a dose dependent contraction in muscle cells enzymatically digested from cat gallbladder. Maximal contraction was obtained at concentration of 10^-9M for CCK-8, 10^-5M for ACh and 20mM for KCl. CCK-8 induced contraction was unaffected in calcium free physiological salt solution (PSS) and was completely blocked by strontium substitution for calcium (p<0.001). In contrast, KCl evoked contraction was blocked in calcium free PSS (p<0.01) but was unaffected by strontium replacement of calcium. The contraction elicited by ACh was only slightly reduced in calcium free PSS (p<0.05) and was unaltered by strontium. Muscle cells permeabilized with saponin contracted in response to inositol 1,4.5-trisphosphate (IP₃) and CCK-8. The contraction was blocked by the calmodulin antagonist CGS 9343B (p<0.001), whereas heparin completely blocked the effect of IP₃ (p<0.001). The protein kinase C (PKC) antagonist H7 had no effect on either agonist. We conclude that CCK-8 induced gallbladder muscle contraction is mediated by IP₃ dependent intracellular calcium release from intracellular stores and a calmodulin dependent pathway; ACh may utilize both extracellular and intracellular calcium. KCl causes muscle contracrion through influx of extracellular calcium and a calmodulin independent machanism.

새앙쥐 강제수영시 부동자세 시간에 대한 Central postsynaptic α₂-Adrenoceptor의 역할에 대한 연구

임병용(Byung-Yong Rhim),김상곤(Sang-Kon Kim),이원식(Won-Suk Lee),홍기환(Ki-Whan Hong) 대한약리학회 1985 대한약리학잡지 Vol.21 No.2

새앙쥐 강제수영 실험에서 부동자세 시간의 단축은 향주도성 행동의 항진이라는 본능적 충동의 유발이라는 가정 아래 중추 noradrenaline neuron에 있어서 α₁- 및 α₂-adrenoceptor의 역할과 관련지어 이 실험을 행하였고 다음과 같은 결론을 얻었다. 1. 새앙쥐를 이용한 강제수영 실험에서 부동자세 시간은 clonidine 및 guanabenz 등과 같은 α₂-agonists에 의하여 용량에 의존하여 단축되었다. B-HT 933 및 oxymetazoline은 용량에 의존하지 않으나 단축시켰다. xylazine에의하여는 오히려 증가되었다. 2.α₁-Agonists 인 cirazoline, amidephrine 및 methoxamine은 부동자세 시간에 일관성 있는 영향을 미치지 아니하였다. 3. Clonidine과guanabenz에 의한 부동자세 시간의 단축은 α₂-antagonists, yohimbine, idazoxan 및 phentolamine 전처치로 봉쇄되었으나 α₁-antagonists, prazosin 및 corynanthine에 의하여는 영향을 받지 아니하였다. 4, d-Amphetamine 투여시 부동자세 시간은 용량에 비례하여 단축되었고, 이러한 단축효과는 yohimbine에 의하여는 길항되었으나 prazosin에 의하여는 영향을 받지 아니하였다. 5. α-methyl-p-tyrosine 이나 reserpine 또는 두 약물을 동시에 전처치 하였을때 clonidine에 의한 부동자세 시간의 단축은 영향을 받지 아니하였다. 6. Desipramine 및 imipramine 같은 항우울제를 장기처치 또는 장기간 저기충격 요법을 가한 새앙쥐에서도 clonidine의 효과는 영향을 받지 아니하였다. 이상의 결과로 보아 새앙쥐의 강제수영 실험에서의 부동자세 시간의 변동은 중추내 noradrenergic neuron의 postsynaptic α₂-adrenoceptor와 밀접한 관련이 있다고 시사되며 이러한 α₂-agonists에 의하여 항진되는 escape-directed behavior는 자기보호를 위한 일종의 충동의 유발로 인한 행동으로 사료된다. 1) In the study of the forced-swimming test in mice (FSM), the duration of immobility posture was dose-dependently shortened by α₂-agonists, clonidine and guanabenz. BH-T 933 and oxymetazoline also decreased it . Xylazine rather increased the immobility duration at low dose. 2) α₁-Agonists, cirazoline, amidephrine and methoxamine, however, showed inconsistent effect on the immobility duration (ID). 3) The decrease in ID by clonidine and guanabenz was antagonized by pretreatment with yohimbine, idazoxan and phentolamine (α₂antagonist), but not by prazosin and corynanthine (α₁-antagonist) .4) The ID in the FSM was shortened dose-dependently by d-amphetamine, and it was also antagonized by yohimbine, but not by prazosin. 5) In the mice pretreated with either α-methyl-p-tyrosine or reserpine, or with combination of both, the decrease in ID was still evoked by clonidine. 6) When the mice were chronically treated with antidepressants (desipramine and imipramine), or with electroconvulsive shock, clonidine still decreased the ID as it did in the control. 7) These results provided the evidences to hypothesize that the change of the ID in the FSM is closely related with the postsynaptie α₂-adrenoceptor located on the central noradrenergic neuron body. Furthermore, it is assumed that this escape-directed behavior enhanced by α₂-adrenoceptor agonist may be the result in some analogy with the incentive of drives which are directed toward the self-preservation.