甘油二酯的作用和激活的蛋白激酶C在α1 a-adrenoceptor-mediated收缩对去甲肾上腺素的分离的大鼠附睾输精管。

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伯特RP,我Chapple CR,马歇尔

甘油二酯的作用和激活的蛋白激酶C在α1 a-adrenoceptor-mediated收缩对去甲肾上腺素的分离的大鼠附睾输精管。

Br J杂志。1996年1月,117 (1):224 - 30。

PubMed ID

8825367 (在PubMed

]

文摘

1。收缩的机制去甲肾上腺素(pEC50 5.6 + / - 0.1)在大鼠附睾的输精管(通过α介导1 a-adrenoceptors)一直在研究功能实验。2。收缩在10(6)米去甲肾上腺素是由甘油二酯强(DAG)激酶抑制剂R 59022 (3 x 10 (7) M)从49 + / - 4%至63 + / - 3%最大响应时间从开始收缩最大响应减少从16 + / - 2 s 9 + / - 1。相同的收缩没有显著的DAG脂肪酶抑制剂,u - 57908, 10(5)米(51 + / - 2%控制和53 + / - 4%的u - 57908)花费的时间也不是从开始收缩最大响应显著改变(17 + / - 1 s轨道控制和16 + / - 1 s的u - 57908)。3所示。浓度收缩对去甲肾上腺素(NA)减少staurosporine (10 (7) M)和选择性蛋白激酶C抑制剂,calphostin C (10 (6) M)从68 + / - 2% (NA, 3 x 10 (6) M) 28 + / - 2%和20 + / - 2%,从94 + / - 2% (NA, 3 x 10(5)米)到50 + / - 2%和44 + / - 2%。收缩到K +(40 + / - 2%最大响应NA)也显著减少staurosporine (10 (7) M)(35 + / - 2%),但不是由calphostin C (43 + / - 3%)。4所示。佛波醇酯、phorbol-12 13-dibutyrate (PDBu),产生了相位的,浓度收缩(10 (7)M - 10(4)米)这是41 + / - 2%的最大响应在10(4)米PDBu NA。 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.

beplay体育安全吗DrugBank数据引用了这篇文章

药物靶点

药物	目标	类	生物	药理作用	行动
Droxidopa	Alpha-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	Alpha-1A肾上腺素能受体	蛋白质	人类	是的	受体激动剂	细节