Diltiazem potentiates the negative inotropic action of nimodipine in heart.

Diltiazem potentiates the negative inotropic action of nimodipine in heart.
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地尔硫卓增强尼莫地平在心脏中的负性肌力作用。

DOI:
10.1016/0006-291x(83)90648-4
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发表时间:
1983
影响因子:
3.1
通讯作者:
Schwartz,A
Schwartz,A
中科院分区:
生物学4区
文献类型:
--
作者:
DePover,A;Grupp,IL;Grupp,G;Schwartz,A

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在Langendorff灌注的大鼠心脏中,尼莫地平增强冠状动脉流量并抑制收缩性。[~ 3 H]尼莫地平(160 Ci/mmol)与狗心肌细胞膜结合的Kd值为0.2 nM。d-顺式地尔硫卓,而不是l-顺式地尔硫卓,一种活性较低的立体异构体,刺激[3 H]尼莫地平(0.17 nM)与肌膜的结合(地尔硫卓的ED 50 = 1.1 μM)。在10 μM d-cis-diltiazem存在下,[3 H]尼莫地平结合位点增加一倍,但表观亲和力没有变化。用250 nM d-顺式地尔硫卓处理灌注的大鼠心脏。对尼莫地平的负性变力反应显著增强(I50,从1.1至0.033 μM)。仅在37°C下观察到药理学和结合作用。地尔硫卓可能以某种方式将低亲和力位点转化为高亲和力位点。
In Langendorff perfused rat hearts, nimodipine enhances coronary flow and inhibits contractility. The binding of [3H]nimodipine (160 Ci/mmol) to sarcolemma isolated from dog heart revealed a KDof 0.2 nM. d-cis-Diltiazem, but not l-cis-diltiazem, a less active stereoisomer, stimulated [3H]nimodipine (0.17 nM) binding to sarcolemmal membranes (ED50for diltiazem = 1.1 μM). In the presence of 10 μM d-cis-diltiazem, [3H]nimodipine binding sites were doubled, but there was no change in the apparent affinity. Perfused rat hearts were treated with 250 nM d-cis-diltiazem. The negative inotropic response to nimodipine was dramatically potentiated (I50, from 1.1 to 0.033 μM). The pharmacological and binding effects were observed only at 37°C. It is possible that diltiazem in some way converts low affinity to high affinity sites.
DOI: 10.1016/0014-5793(82)80835-1
发表时间: 1982
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影响因子: 3.5
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发表时间: 1982
影响因子: 3.1
作者:
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通讯作者: Schwartz,A