Pharmacological properties of voltage-dependent calcium channels in functional microvessels isolated from rat brain
Pharmacological properties of voltage-dependent calcium channels in functional microvessels isolated from rat brain
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大鼠脑功能微血管中电压依赖性钙通道的药理学特性
DOI：
10.1007/bf00167047
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发表时间：
1989
期刊：
影响因子：
--
通讯作者：
T. Godfraind
中科院分区：
文献类型：
--
作者：
N. Morel;T. Godfraind
本实验研究了大鼠脑内微血管电压操纵性钙通道。通过测量灌流微血管的内径来评估对KCl去极化的收缩反应性。用~ 3 H（+）PN 200-110 [异丙基-4-（2，1，3-苯并二唑-4-基）-1，4-二氢-2，6-二甲基-5-甲氧羰基-吡啶-3-羧酸酯]鉴定和表征了与钙通道相关的二氢吡啶受体位点。血管收缩是可逆的，并可被尼莫地平消除。与3 H（+）PN 200-110的结合研究表明，在37°C下，在NaCl培养基中孵育的微血管中，存在一类特异性、立体选择性和电压依赖性结合位点，其结合（+）PN 200-110的KD为88 ± 6.6 pmol l−1。当微血管在KCl培养基中孵育时，表观KD值降低至35 ± 2 pmol l−1。Bmax无显著变化。KCl的作用与Na浓度的伴随变化无关。各种二氢吡啶衍生物抑制3 H（+）PN 200-110结合的效力与其在平滑肌制剂中的药理学效力一致。PN 200-110和尼莫地平的作用具有立体选择性。PN 200-110和尼莫地平的Ki值在去极化制剂中增加，而硝苯地平的效力不变。维拉帕米仅部分抑制3 H（+）PN 200-110结合。地尔硫卓的作用是立体选择性的：地尔硫卓的（+）-顺式异构体增强与PN 200- 110的结合，而（-）-顺式异构体对PN 200- 110的结合抑制作用很弱。结果表明，离体脑微血管具有功能性电压操纵性钙通道，其中含有二氢吡啶类钙通道阻滞剂的电位调节受体，其特征与其他组织中所描述的相似。
SummaryVoltage-operated calcium channels were studied in rat intracerebral microvessels. The contractile reactivity to KCI-depolarization was assessed by the measurement of internal diameter of superfused microvessels. Dihydropyridine receptor sites associated with calcium channels were identified and characterized using 3H(+)PN 200-110 [isopropyl-4-(2,1,3-benzodiazol-4-yl)-1,4-dihydro-2,6-dimethyl-5-methoxycarbonyl-pyridine-3-carboxylate].Depolarization induced by high-KCI solution produced a marked reduction of the internal diameter of cerebral microvessels which was associated with the appearance of rhythmic activity. The vessel contraction was reversible and abolished by nimodipine. Binding studies with 3H(+)PN 200-110 revealed the existence of a single class of specific, stereoselective and voltage-dependent binding sites which bound (+)PN 200-110 with a KD of 88 ± 6.6 pmol l−1 at 37°C in microvessels incubated in NaCl medium. When microvessels were incubated in KCI-medium, the apparent KD value was reduced to 35 ± 2 pmol l−1. Bmax was not significantly changed. The effect of KCI was not related to concomitant changes in the Na concentration. The potency of various dihydropyridine derivatives in inhibiting 3H(+)PN 200-110 binding was in agreement with their pharmacological potency in smooth muscle preparations. The effect of PN 200-110 and of nimodipine was stereoselective. Ki values of PN 200-110 and of nimodipine were increased in depolarized preparations, while nifedipine's potency was unchanged. Verapamil was only a partial inhibitor of 3H(+)PN 200-110 binding. The effect of diltiazem was stereoselective: the (+)-cis isomer enhanced the binding and the (−)-cis isomer of diltiazem poorly inhibited the binding of PN 200-110.Results showed that isolated cerebral microvessels possess functional voltage-operated calcium channels, which contain potential-modulated receptors for dihydropyridine calcium entry blockers with characteristics similar to those described in other tissues.
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钙通道拮抗剂 ( )-[3H]PN200-110 与完整培养的 PC12 细胞的去极化依赖性结合。
DOI：
--
发表时间：
1986
期刊：
The Journal of pharmacology and experimental therapeutics
影响因子：
--
作者：
Greenberg,DA;Carpenter,CL;Messing,RO
通讯作者：
Messing,RO
[3H]尼群地平与冠状动脉和心脏膜的特异性结合与药理作用的关系。
DOI：
10.1016/0006-291x(82)91838-1
发表时间：
1982
影响因子：
3.1
作者：
DePover,A;Matlib,MA;Lee,SW;Dubé,GP;Grupp,IL;Grupp,G;Schwartz,A
通讯作者：
Schwartz,A
药物-受体相互作用的定量分析：I.动力学和平衡特性的测定。
影响因子：
6.1
作者：
Weiland,GA;Molinoff,PB
通讯作者：
Molinoff,PB
电压依赖性尼群地平与心脏肌膜囊泡的结合。
影响因子：
3.6
作者：
Kamp,TJ;Miller,RJ
通讯作者：
Miller,RJ
[3H]螺哌啶醇结合位点的表征。
影响因子：
5.8
作者：
Luedtke,RR;Molinoff,PB
通讯作者：
Molinoff,PB