Relationship between β‐adrenoceptors and calcium channels in human ventricular myocardium
Relationship between β‐adrenoceptors and calcium channels in human ventricular myocardium
复制标题
人心室心肌β-肾上腺素受体与钙通道的关系
DOI：
--
复制
发表时间：
1987
影响因子：
7.3
通讯作者：
A. Kaumann
中科院分区：
文献类型：
--
作者：
D. Ferry;A. Kaumann
1研究了人心室肌钙通道中肾上腺素受体与1，4-二氢吡啶类化合物饱和结合位点的化学计量关系。膜颗粒由接受心脏直视手术的患者的心脏标本制备。患者患有肥厚型梗阻性心肌病（HOCM）或二尖瓣疾病。2使用[3 H]-哌唑嗪和[125 I]-2-β-羟基-3-碘苯基乙基氨乙基四氢萘酮（[125 I]-HEAT）作为标记物，我们仅检测到α1-肾上腺素受体的边缘密度，与疾病无关。[3 H]-萝芙木碱未检测到α2-肾上腺素受体。3在HOCM患者中，我们估计了72 ± 10 fmol mg−1（n = 12）用[3 H]-（-）-二氢烯丙洛尔标记的β-肾上腺素受体和74 ± 5 fmol mg−1（n = 2）用[125 I]-（-）-碘氰基吲哚洛尔标记的β-肾上腺素受体;[3 H]-（-）-二氢烯丙洛尔的平衡解离常数KD为1.2 ± 0.2 nmol l−1，[125 I]-（-）-碘氰基吲哚洛尔的平衡解离常数KD为7 ± 1 pmol l−1。在二尖瓣疾病患者中，我们估计[3 H]-（-）-二氢阿普洛尔标记的剂量为84 ± 11 fmol mg−1（n = 3），[125 I]-（-）-碘氰基吲哚洛尔标记的剂量为66 ± 13 fmol mg−1（n = 2）。[3 H]-（-）-二氢阿普洛尔的KD值为1.8 ± 0.6 nmol l−1，[125 I]-（-）-碘氰基吲哚洛尔的KD值为8 ± 2 pmol l−1。[4]在14例HOCM患者中，我们估计有107 ± 12 fmol mg−1钙通道位点被[3 H]-尼莫地平标记，KD为280 ± 4 pmol l−1。在5例二尖瓣疾病患者中，用[3 H]-尼莫地平标记的钙通道位点的密度为78 ± 5 fmol mg−1，KD为290 ± 20 pmol l−1，在HOCM患者中，用苯并恶二唑1标记的钙通道位点的密度，4-二氢吡啶（[3 H]-（+）-PN 200-110）是[3 H]-尼莫地平标记的1.6倍，KD为84 ± 11 pmol l−1。5在一组4名HOCM患者中，钙通道用[125 I]-碘平标记，部位密度是[3 H]-（+）-PN 200 - 11-标记部位密度的1.37 ± 0.07倍。[125 I]-碘平的KD值为246 ± 16 pmol−1。（+）-PN 200 - 110作为[125 I]-碘平结合的竞争者的效力约为（-）-PN 200 - 110的100倍。6在HOCM组中，β-肾上腺素受体密度与钙通道密度之间存在显著相关性，而在二尖瓣组中没有发现这种相关性，这并不能证明β-肾上腺素受体密度与钙通道密度之间存在因果关系。然而，由于β-肾上腺素受体介导的儿茶酚胺的正性变力作用与钙通道的开放相关，这表明β-肾上腺素受体和钙通道的密度可以共同调节。
1 The stoichiometric relationship between adrenoceptors and saturable binding sites for 1,4‐dihydropyridines in calcium channels was investigated in human ventricular myocardium. Membrane particles were prepared from heart specimens of patients undergoing open heart surgery. The patients suffered from hypertrophic obstructive cardiomyopathy (HOCM) or mitral valve disease. 2 Using [3H]‐prazosin and [125I]‐2‐β‐hydroxy‐3‐iodiphenyl‐ethyl‐aminoethyl tetralone ([125I]‐HEAT) as labels we detected only a marginal density of α1‐adrenoceptors, regardless of disease. No α2‐adrenoceptors were detected with [3H]‐rauwolscine. 3 In HOCM patients we estimated 72 ± 10 fmol mg−1 (n = 12) β‐adrenoceptors labelled with [3H]‐(‐)‐dihydroalprenolol and 74 ± 5 fmol mg−1 (n = 2) β‐adrenoceptors labelled with [125I]‐(‐)‐iodocyanopindolol; the equilibrium dissociation constants KD, were 1.2 ± 0.2 nmol l−1 for [3H]‐(‐)‐dihydroalprenolol and 7 ± 1 pmol l−1 for [125I]‐(‐)‐iodocyanopindolol. In patients with mitral valve disease we estimated 84 ± 11 fmol mg−1 (n = 3) labelled with [3H]‐(‐)‐dihydroalprenolol and 66 ± 13 fmol mg−1 (n = 2) labelled with [125I]‐(‐)‐iodocyanopindolol. The KD values were 1.8 ± 0.6 nmol l−1 for [3H]‐(‐)‐dihydroalprenolol and 8 ± 2 pmol l−1 for [125I]‐(‐)‐iodocyanopindolol. 4 In 14 HOCM patients we estimated 107 ± 12 fmol mg−1 calcium channel sites labelled with [3H]‐nimodipine with a KD of 280 ± 4 pmol l−1. In 5 patients with mitral valve disease the density of calcium channel sites labelled with [3H]‐nimodipine was 78 ± 5 fmol mg−1 with a KD of 290 ± 20 pmol l−1, In HOCM patients the density of calcium channel sites labelled with the benzoxadiazol 1, 4‐dihydropyridine ([3H]‐(+)‐PN 200–110) was 1.6 fold of that labelled with [3H]‐nimodipine with a KD of 84 ± 11 pmol l−1. 5 In a group of 4 HOCM patients in which calcium channels were labelled with [125I]‐iodipine, the density of sites was 1.37 ± 0.07 fold the density of sites labelled by [3H]‐(+)‐PN 200‐11‐. The KD value of [125I]‐iodipine was 246 ± 16 pmol−1. (+)‐PN 200‐110 was approximately 100 fold more potent than (‐)‐PN 200‐110 as a competitor of [125I]‐iodipine binding. 6 For the HOCM group a significant correlation was found between β‐adrenoceptor density and calcium channel density, whereas in the mitral valve group no such correlation was found. This does not prove that there is causal interaction leading to a relationship between the density of β‐adrenoceptors and calcium channels. However, because positive inotropic effects of catecholamines mediated by β‐adrenoceptors are associated with opening of calcium channels, this suggests that the density of both β‐adrenoceptors and calcium channels could be co‐regulated.
登录
查看更多内容
二氢吡啶 202-791 立体异构体的钙通道激动剂和拮抗剂作用。
DOI：
10.1016/0006-291x(85)90393-6
发表时间：
1985
影响因子：
3.1
作者：
Kongsamut,S;Kamp,TJ;Miller,RJ;Sanguinetti,MC
通讯作者：
Sanguinetti,MC
心脏 1,4-二氢吡啶受体/钙通道复合物的纯化。
DOI：
10.1016/0006-291x(85)90563-7
发表时间：
1985
影响因子：
3.1
作者：
Rengasamy,A;Ptasienski,J;Hosey,MM
通讯作者：
Hosey,MM
影响因子：
20.1
作者：
SIMPSON, P
通讯作者：
SIMPSON, P
人心脏β-肾上腺素能受体：通过直接放射性配体结合描绘的亚型异质性。
影响因子：
6.1
作者：
Stiles,GL;Taylor,S;Lefkowitz,RJ
通讯作者：
Lefkowitz,RJ
影响因子：
158.5
作者：
BRISTOW, MR;GINSBURG, R;STINSON, EB
通讯作者：
STINSON, EB