二酰基甘油和蛋白激酶C激活在α 1a肾上腺素受体介导的大鼠附睾输精管去甲肾上腺素收缩中的作用。

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伯特RP，查普CR，马歇尔I

二酰基甘油和蛋白激酶C激活在α 1a肾上腺素受体介导的大鼠附睾输精管去甲肾上腺素收缩中的作用。

中华药物学杂志，1996 01;17(1):224-30。

PubMed ID

8825367 (PubMed视图

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摘要

1.功能性实验研究了大鼠附睾输精管去甲肾上腺素(pEC50 5.6 +/- 0.1)收缩的机制(通过α 1a肾上腺素受体介导)。2.二酰基甘油(DAG)激酶抑制剂R 59022 (3 x 10(-7) M)增强了10(-6)M时去甲肾上腺素的收缩，从最大反应的49 +/- 4%增加到63 +/- 3%，从收缩开始到最大反应的时间从16 +/- 2秒减少到9 +/- 1秒。DAG脂肪酶抑制剂u - 57908, 10(-5) M(51 +/- 2%对照组和53 +/- 4% u - 57908存在时)没有显著增强同样的收缩，从收缩开始到最大反应所花的时间也没有显著改变(17 +/- 1 s对照组和16 +/- 1 s u - 57908存在时)。3.staurosporine (10(-7) M)和选择性蛋白激酶C抑制剂calphostin C (10(-6) M)分别从68 +/- 2% (NA, 3 x 10(-6) M)降低到28 +/- 2%和20 +/- 2%，从94 +/- 2% (NA, 3 x 10(-5) M)分别降低到50 +/- 2%和44 +/- 2%。staurosporine (10(-7) M)(35 +/- 2%)也显著降低了K+的收缩(对NA的最大反应为40 +/- 2%)，但calphostin C(43 +/- 3%)没有降低。4.磷酚酯，磷酚-12,13-二丁酸酯(PDBu)，产生了一个相位的，浓度依赖的收缩(10(-7)M - 10(-4) M)，是10(-4)M PDBu对NA最大响应的41 +/- 2%。 The contraction to PDBu (10(-5) M) was reduced by calphostin C (10(-6) M) from 33 +/- 5% to 4 +/- 1% maximum response to NA. 5. Non-cumulative contractions to NA (10(-8) M - 10(-4) M) were abolished in Ca(2+)-free Krebs solution containing EGTA (1 mM) and were reduced in the presence of nifedipine (10(-6)M) in normal Krebs solution by 91 +/- 2% at 10(-4)M NA. The contraction to PDBu (10(-5)M, 33 +/- 5% maximum response to NA) was also abolished in Ca(2+)-free Krebs solution containing EGTA (1 mM) or by the presence of nifedipine (10(-6)M) in normal Krebs solution. 6. When NA (10(-4)M) was added to vasa deferentia in Ca(2+)-free Krebs solution containing EGTA (1 mM), following its wash out (and with EGTA later removed from the Krebs solution), readdition of Ca2+ (2.5 mM) to the Krebs solution produced no response. Cyclopiazonic acid (10(-5)M), which can deplete Ca2+ from intracellular stores, also produced no contraction. Therefore influx of extracellular Ca2+ is not a consequence of depletion of intracellular Ca2+ stores (capacitative Ca2+ influx). 7. Pre-incubation of tissues for 30 min with either cyclopiazonic acid (10(-5)M) or ryanodine (10(-4)M), which can both deplete intracellular Ca2+ stores, did not reduce the contractions to NA (3 x 10(-6)M). Pre-incubation of vasa deferentia with cyclopiazonic acid (1 or 3 min, when any rise in [Ca2+]i produced by cyclopiazonic acid might still exist) did not potentiate the contraction to PDBu (10(-5)M). Thus mobilization of intracellular Ca2+ may not be required for the activation of protein kinase C involved in these contractions. 8. In conclusion, the contraction of the rat epididymal vas deferens to NA mediated by alpha 1A-adrenoceptors appears to depend upon activation of protein kinase C by diacylglycerol, resulting in the influx of extracellular Ca2+ through voltage-gated Ca2+ channels. There was no evidence for a role of inositol trisphosphate in the contraction to noradrenaline in this tissue.

引用本文的药物库数据

药物靶点

药物	目标	种类	生物	药理作用	行动
Droxidopa	α - 1a肾上腺素能受体	蛋白质	人类	是的	受体激动剂	细节
去甲肾上腺素	α - 1a肾上腺素能受体	蛋白质	人类	是的	受体激动剂	细节