• 한국의학물리학회지:의학물리
• /
• 제8권1호
• /
• pp.3-15
• /
• 1997

Adrenal chromaffin cells secrete catecholamine in response to acetylcholine. The secretory response has absolute requirement for extracellular calcium, indication that $Ca^{2+}$ influx through voltage dependent $Ca^{2+}$ channel (VDCC) is the primary trigger of the secretion cascade. Although the existence of various types of $Ca^{2+}$ channels has been explored using patch clamp technique in adrenal chromaffin cells, the contribution of different types of $Ca^{2+}$ channels to catecholamine secretion remains to be established. To investigate the quantative contribution of different types of $Ca^{2+}$ channels to cate-cholamine secretion, $Ca^{2+}$ current($I_{Ca}$) and the resultant membrane capacitance increment($\Delta{C}_{m}$) were simultaneoulsy measured. Software based phasor detector technique was used to monitor $\Delta{C}_{m}$. After blockade of L type VDCC with nicardipine (1$\mu$M), $I_{ca}$ was blocked to 43.85$\pm$6.72%(mean$\pm$SEM) of control and the resultant ㅿC$_{m}$ was reduced ot 30.10$\pm$16.44% of control. In the presence of nicardipine and $\omega$-conotoxin in GVIA(l$\mu$M), an N type VDCC antagonist, $I_{ca}$ was blocked to 11.62$\pm$2.96% of control and the resultant $\Delta{C}_{m}$ was reduced to 26.13$\pm$8.25% of control. Finally, in the presence of L, N, and P type $Ca^{2\pm}$ channel antagonists(nicardipine, $\omega$-Conotoxin GVIA, and $\omega$-agatoxin IVA, respectively), $I_{ca}$ and resultant $\Delta{C}_{m}$ were almost completely blocked. From the observation of parallel effects of $Ca^{2+}$ channel antagonists on $I_{ca}$ and $\Delta{C}_{m}$, it was concluded that L, N, and also P type $Ca^{2+}$ channels served and $Ca^{2+}$ source for exocytosis and no difference was observed in their efficiency to evoke exocytosis amost L, N, and P type $Ca^{2+}$ channels.

• The Korean Journal of Physiology and Pharmacology
• /
• 제6권2호
• /
• pp.87-91
• /
• 2002

The aim of this study was to investigate the role of $Ca^{2+}-channel$ blockers in norepinephrine (NE) release from rat hippocampus. Slices and synaptosomes were incubated with $[^3H]-NE$ and the releases of the labelled products were evoked by 25 mM KCl stimulation. Nifedipine, diltiazem, nicardipine, flunarizine and pimozide did not affect the evoked and basal release of NE in the slice. But, diltiazem, nicardipine and flunarizine decreased the evoked NE release with a dose-related manner without any change of the basal release from synaptosomes. Also, a large dose of pimozide produced modest decrement of NE release. ${\omega}-conotoxin$ (CTx) GVIA decreased the evoked NE release in a dose-dependent manner without changing the basal release. And ${\omega}-CTxMVIIC$ decreased the evoked NE release in the synaoptosomes without any effect in the slice, but the effect of decrement was far less than that of ${\omega}-CTxGVIA.$ In interaction experiments with ${\omega}-CTxGVIA,\;{\omega}-CTxMVIIC$ slightly potentiated the effect of ${\omega}-CTxGVIA$ on NE release in the slice and synaptosomal preparations. These results suggest that the NE release in the rat hippocampus is mediated mainly by N-type $Ca^{2+}-channels,$ and that other types such as L-, T- and/or P/Q-type $Ca^{2+}-channels$ could also be participate in this process.

• Biomolecules & Therapeutics
• /
• 제1권1호
• /
• pp.1-8
• /
• 1993

It has been known that calcium antagonists also inhibit the radioligand binding to muscarinic and $\alpha$-adrenergic receptors and, in case of verapamil, these inhibitions may play a role in the effects of verapamil on the heart. In this study, the effects of nicardipine, nifedipine, nimodipine, diltiazem and verapamil on the binding of [$^3H$]dihydroalprenolol (DHA) to dog cardiac ${\beta}$-adrenergic receptors were examined. A single uniform [$^3H$]DHA binding site ($K_D/= 5nM\;and\;B_{max}=2600$ fmol/mg protein) was identified in dog cardiac sarcolemma. [$^3H$]DHA binding was not affected by the usual therapeutic concentrations of these calcium antagonists (nanomolar range) but in the "nonspecific"concentration ranges ($28-180{\mu}m$) these drugs inhibited [$^3H$]DHA binding to $\beta$-adrenergic receptors. Nicardipine, nifedipine, nimodipine and diltiazem competed for [$^3H$]DHA binding to ${\beta}$-adrenergic receptors with dissociation constants ($K_i$) of $28{\mu}m,\' 74{\mu}m, 39{\mu}m \;and \;35{\mu}m,$ respectively. Verapamil ($K_i=176.5 {\mu}m$) was less potent inhibitor than other drugs and this inhibition was noncompetitive; the maximal binding capacity ($B_{max}$) $300 {\mu}m$ verapamil without change in the apparent dissociation constant (4K_D$) for DHA. These results indicate that the inhibitory action of calcium antagonists at high concentrations on ${\beta}$-adrenergic receptors is not involved in the therapeutic effects of these drugs by the calcium channel blocking action.

• 한국의학물리학회지:의학물리
• /
• 제12권1호
• /
• pp.59-70
• /
• 2001

부신수질 크로마핀세포는 아세틸콜린에 반응하여 카테콜아민을 분비한다. 카테콜아민이 분비되기 위하여는 세포외 칼슘이 절대적으로 필요한데 이는 막전압 의존성 칼슘통로를 통하여 칼슘이 세포 속으로 유입되어야 분비기전이 시작됨을 시사한다. 부신수질 크로마핀 세포를 단일세포로 분리한 후 패치클람프 테크닉을 적용하여 여러 종류의 칼슘통로가 존재한다는 것이 알려져 있으나 아직 종이 달라짐에 따라 다른 칼슘통로가 존재하는 지 여부가 확실하지 않다. 그러므로 본 연구에서는 흰쥐 부신수질 크로마핀 세포를 대상으로 하여 단일 세포 패치클람프 테크닉을 적용하여 이 세포에 존재하는 다양한 칼슘통로의 존재를 확인하고자 하였다. L형 칼슘통로 억제제인 nicardipine, N형 칼슘통로 억제제인 $\omega$-CgTx GVIA, P형 칼슘통로 억제제인 $\omega$-AgaTx IVA를 사용하여 L형, N형, P형 칼슘통로가 흰쥐 부신수질 세포에 존재함을 확인하였고 개개의 칼슘통로가 전체 칼슘전류에 기여하는 정도는 L형 >N형> P형이었다.

• 약학회지
• /
• 제33권3호
• /
• pp.167-174
• /
• 1989

KR-1008 and KR-30006 are 1,4-dihydropyridine derivatives, new vasodilatory calcium antagonists from KRICT. Calcium antagonistic properties of the compounds were studied in the isolated heart (Langendorff preparation), pulmonary artery (vasodilation), and in the papillary muscle (negative inotropic effect) of the guinea pig. Antihypertensive effect were also investigated after i.v. or oral administration in the SHR (spontaneously hypertensive rat). They produced a sigificant inhibition of Ca-induced contraction in the guinea pig pulmonary artery at the concentrations of above $10^{-8}M$. The negative inotropic effect of the electrically stimulated papillary muscle appeared from the concentration of $10^{-6}M$, which is about hundred times higer than the concentration of vasodilation effect. Left ventricular pressure also decreased from the concentration of $3\;{\times}\;10^{-6}M$ in KR-1008 and KR-3006 in the Langendorff heart preparations. Coronary flow rate increased from $10^{-6}M$ in KR-1008 and nicardipine and appeared no change in KR-30006. The antihypertensive effect of KR-1008 (EC 20: $2.9\;{\mu}g/kg$) was potent more than nicardipine (EC 20: $3.4\;{\mu}g/kg$) and than Kr-30006 (EC 20: $6.8\;{\mu}g/kg$) was, after i.v. bolus injection in the anesthetized SHR. The antihypertensive effect in the conscious SHR appeared 30 minutes after oral administration of 10 mg/kg and persisted 4 hrs in KR-1008 and 12 hrs in KR-30006. Heart rate tended to increase for 0.5-1 hr after oral administration of the test compounds.

• The Korean Journal of Physiology
• /
• 제30권1호
• /
• pp.21-31
• /
• 1996

To investigate the mechanisms of increased endothelium-dependent contraction by acetylcholine in hypertensive rats, the relationship between endothelium-dependent contraction by acetylcholine and blood pressure was studied in spontaneously hypertensive rats (SHR), one-kidney, one clip Goldblatt hypertension (1K,1C-GBH) rats, and Wistar-Kyoto rats (WKY). SHR were treated orally with enalapril or nicardipine in order to prevent development of hypertension or suppress the developed hypertension. 1K,1C-GBH rats were made by renal artery stenosis with contralateral nephrectomy in 8 week-WKY. 1. Endothelium-dependent contractions by acetylcholine $(10^{-6}{\sim}10^{-5}\;M)$ in SHR were significantly greater than those in WKY. 2. Chronic treatment with enalapril or nicardipine reduced the endothelium-dependent contraction in SHR 3. The degree of reduction of endothelium-dependent contraction was greater in SHR which was prevented from developing hypertension than in SHR of which high blood pressure was suppressed. 4. In aortic rings from 1K,1C-GBH rats, endothelium-dependent contractions by acetylcholine were augmented as compared with WKY. 5. There is good relationship between the value of blood pressure and magnitude of endothelium-dependent contraction. Thus, it is suggested that increased endothelium-dependent contraction in hypertensive rats may he due to the high blood pressure and endothelium-dependent contraction may not be a cause of the initiation of hypertension in SHR.

• Childhood Kidney Diseases
• /
• 제2권2호
• /
• pp.125-132
• /
• 1998

목 적 : 초기만성신부전증에서 저단백식이를 항고혈압제와 병행 투여하였을 때 저단백식이 단독 투여 때보다 만성신부전의 진행속도 및 혈압조절에 어떠한 영향을 주는지 알기 위하여 저자들은 실험동물 백서를 이용하여 excision remnant kidney model로 만성 신부전을 유발시켰다. 방 법 : 5/6신 절제술로 만성 신부전을 유발시킨 백서를 순술 제 7일부터 무작위로 저단백식이 ($6\%$단백식이) 단독투여군, 저단백식이 enalapril 투여군 (식수 1 L당 50 mg),저단백식이 nicardipine 투여군 (사료 g당 0.2mg)로 나누어 신절제술후 4주, 12주, 16주에 단백뇨의 변화, 신 조직의 mesangial matrix expansion score 및 morphometric analysis로 분석한 사구체용적의 변화를 비교 분석하였다. 결 과 : 1)저단백식이 단독투여군은 신절제술후 계속 혈압이 증가됨을 볼 수 있었으며, 저단백식이 항고혈압제투여군은 신절제술후 8주부터 항고혈압제 투여 7주 후부터 저단백식이 단독투여군에 비해 혈압이 조절되기 시작하였다. 2)신절제술후 16주 째의 24시간 뇨단백은 세군 모두 크게 증가되지 않았으나 저단백식이 enalapril 투여군, 저단백식이 nicardipine투여군은 저단백식이 단독투여군에 비해 24시간 뇨단백의 양이 통계적으로 의미있게 낮았다. 3) 신절제술후 16주째 크레아티닌 청소 율은 저단백식이 단독투여군은 $1.57{\pm}0.11\;mL/min$, 저단백식이 enalapril 투여군 $1.37{\pm}0.14\;mL/min$, 저단백식이 nicardipine 투여군 $1.11{\pm}0.16\;ml/min$ 이었다. 4) 저단백식이 단독투여군의 잔여 신장무게는 신절제술후 4주 $1.33{\pm}0.04g$, 12주 $1.45{\pm}0.05g$, 16주 $1.44{\pm}0.16g$으로 12주 이후 잔여 신장무게의 증가를 관찰할 수 없었다. .신절제술후 16주에 관찰한 저단백식이 단독투여군과 저단백식이 항고혈압제투여군간의 잔여 신장무게는 통계적인 차이는 없었다. 5) 저단백식이 단독투여군의 mesangial matrix expansion score는 12주째 증가소견을 보였고 저단백식이 항고혈압제투여군은 항고혈압제 투여에도 불구하고 12주 이후 mesangial matrix expansion score의 의미있는 증가소견이 없었고 세군 간의 차이도 없었다. 6) 저단백식이 단독투여군의 사구체용적은 12주째 증가소견을 보였고 저단백식이 항고혈압제 투여군은 항고혈압제 투여에도 불구하고 12주 이후 사구체용적의 의미있는 증가소견이 없었고 세군 간의 차이도 없었다. 결 론 : 초기만성신부전증에서 저단백식이는 혈압을 조절시키지 못하였고 저단백식이 항고혈압제투여군은 저단백식이 단독투여군보다 혈압조절 및 단백뇨의 감소 소견은 유의한 차이를 보였으나, mesangial matrix expansion score,대상성 사구체비대는 통계적으로 유의한 차이를 보이지 않았다. 그러므로 만성신부전의 진행을 지연시키는데 있어서 저단백식이와 함께 항고혈압제를 추가하였을 때 항고혈압제에 의한 추가적인 지연 효과는 관찰되지 않았다.

• 한국응용약물학회:학술대회논문집
• /
• 한국응용약물학회 1994년도 춘계학술대회 and 제3회 신약개발 연구발표회
• /
• pp.284-284
• /
• 1994

Pentazocine은 opioid 수용체에 대한 흥분작용과 길항작용을 겸유한 opioid계 약물로 알려져 있다. 본 연구에서 흰쥐 적출 관류부신 으로 부터 pentazocine의 catecholamine (CA) 분비작용을 관찰하여 그 기전을 규명하고 또한 다른 opioid의 작용과 비교하여 얻어진 결과는 다음과 같다. Pentazocine (30-300$\mu\textrm{g}$)을 부신정맥내에 주사하였을때 현저한 용량 의존성의 CA 분비 작용을 나타내었다. Pentazocine의 이러한 CA 분비작용은 chlorisondamine ($10^{-6}$M), naloxone (1.22 $\times$ $10^{-7}$M), morphine (1.73 $\times$ $10^{-5}$M). enkephalin (9.68 $\times$$10^{-6}$M), nicardipine ($10^{-6}$M) 및 TMB-8 ($10^{-5}$M)등의 전처치로 뚜렷이 억제되었으나 pirenzepine (2 $\times$ $10^{-6}$M)의 전처치에 의해서는 영향을 받지 않았다. $Ca^{++}$-free Krebs 용액으로 30분간 관류한 후에 pentazocine의 CA 분비작용은 현저한 감소를 나타내었다. Pentazocine (1.75 $\times$ $10^{-4}$M)을 20분간 관류시킨 후에 ACh (5.32 $\times$ $10^{-3}$M)과 DMPP ($10^{-4}$M)에 의한 CA 분비작용이 의의있게 감약되었다.

• Archives of Pharmacal Research
• /
• 제18권6호
• /
• pp.402-409
• /
• 1995

The effects of calcium channel blockers (CAB's) verapamil, diltiazem and nicardipine, on erythrocyte ghost membranes have been studied. Using the fluorospectroscopic method, it was observed that the fluidity of the inner layer of ghost membranes was increased with an increase of drug concentrations but did not any changes in the fluidity of the outer layer. These drugs showed protectuve effect against hypotonic hemolysis of erythrocytes. Thus, the expansion of surface area in response to corpuscular volume of erythrocytes in the presence of CAB's is seemed to play an important role in protecting hypotonic hemolysis of erythrocytes.

• 대한약리학회지
• /
• 제29권1호
• /
• pp.43-55
• /
• 1993

흰쥐 관류부신에서 histamine의 catecholamine (CA) 분비작용의 특성과 기전을 규명코자 연구한 결과는 다음과 같다. Histamine $(37.5{\sim}150\;{\mu}g)$을 부신정맥내에 주사 하였을 때 현저한 용량 의존성의 CA 분비작용을 나타내었다. 그러나 histamine $(150\;{\mu}g)$을 120분 간격으로 반복 투여시 제 3차 투여시부터는 CA 분비효과가 뚜렷이 감소하였다. 즉, histamine의 반복투여로 인한 반응급강현상을 관찰할 수 있었다. Histamine의 CA 분비작용은 chlorisondamine, diphenhydrarmine, ranitidine, $Ca^{++}-free$ Krebs 용액의 관류, nicardipine 및 TMB-8 등의 전처치로 유의하게 억제 되었으나 pirenzepine의 전처치에 의해서는 별다른 영향을 받지 않았다. 더우기 histamine $(6.8{\times}10^{-5}M)$으로 30분간 관류시킨 후에 ACh $(50{\mu}g)$의 CA 분비작용이 상당히 억제됨을 나타내었다. 이상과 같은 연구 결과로 보아 histamine은 흰쥐 적출관류 부신에서 현저한 CA 분비작용을 나타내었으며 칼슘 의존성이었다. 이러한 CA 분비작용은 $H_1-$ 및 $H_2-$ 양수용체의 활성화를 통해서 일어나며 또한 부신의 nicotine 수용체와도 관련성이 있는 것으로 사료된다.