Differential inhibition of secretagogue-stimulated sodium uptake in adrenal chromaffin cells by activation of D4 and D5 dopamine receptors.

Differential inhibition of secretagogue-stimulated sodium uptake in adrenal chromaffin cells by activation of D4 and D5 dopamine receptors.
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通过激活 D4 和 D5 多巴胺受体,差异性抑制肾上腺嗜铬细胞中促分泌剂刺激的钠摄取。

DOI:
10.1046/j.1471-4159.1996.67051960.x
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发表时间:
1996
影响因子:
4.7
通讯作者:
Senogles,SE
Senogles,SE
中科院分区:
医学2区
文献类型:
--
作者:
Dahmer,MK;Senogles,SE

文献摘要

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最近的研究表明,D1选择性和D2选择性多巴胺受体激动剂通过受体亚型抑制牛肾上腺嗜铬细胞的儿茶酚胺分泌和Ca 2+摄取,我们通过PCR鉴定为D5,D1样多巴胺受体亚家族的成员,和D4,D2样多巴胺受体亚家族的成员。本研究的目的是确定D5或D4受体的激活是否抑制Na+的内流,这可以解释多巴胺激动剂对分泌和Ca 2+摄取的抑制。D1-选择性激动剂优先抑制二甲基苯基哌嗪-(DMPP)和藜芦啶刺激的22 Na+流入嗜铬细胞。D1选择性激动剂氢溴酸氯-APB(CI-APB; 100 µM)和SKF-38393(100 µM)分别抑制DMPP刺激的Na+摄取87.5 ± 2.3%和59.7 ± 4.5%,而D2选择性激动剂溴隐亭(100 µM)仅抑制Na+摄取22.9 ± 5.0%。100 µ MCI-APB或溴隐亭分别抑制藜芦定刺激的Na+摄取95.1 ± 3.2和25.7 ± 4.7%。CI-APB的作用具有浓度依赖性。获得了抑制DMPP和藜芦碱刺激的Na+摄取的相似IC 50(> 18 µM)。添加8-溴环AMP(1 mM)对DMPP或藜芦碱刺激的Na+摄取均无影响。这些观察结果表明,D1选择性激动剂以环AMP非依赖性方式抑制促分泌素刺激的Na+摄取。
Recent studies have demonstrated that D1‐selective and D2‐selective dopamine receptor agonists inhibit catecholamine secretion and Ca2+uptake into bovine adrenal chromaffin cells by receptor subtypes that we have identified by PCR as D5, a member of the D1‐like dopamine receptor subfamily, and D4, a member of the D2‐like dopamine receptor subfamily. The purpose of this study was to determine whether activation of D5 or D4 receptors inhibits influx of Na+, which could explain inhibition of secretion and Ca2+uptake by dopamine agonists. D1‐selective agonists preferentially inhibited both dimethylphenylpiperazinium‐ (DMPP) and veratridine‐stimulated22Na+influx into chromaffin cells. The D1‐selective agonists chloro‐APB hydrobromide (CI‐APB; 100 µM) and SKF‐38393 (100 µM) inhibited DMPP‐stimulated Na+uptake by 87.5 ± 2.3 and 59.7 ± 4.5%, respectively, whereas the D2‐selective agonist bromocriptine (100 µM) inhibited Na+uptake by only 22.9 ± 5.0%. Veratridine‐stimulated Na+uptake was inhibited 95.1 ± 3.2 and 25.7 ± 4.7% by 100 µMCI‐APB or bromocriptine, respectively. The effect of CI‐APB was concentration dependent. A similar IC50(∼18 µM) for inhibition of both DMPP‐ and veratridine‐stimulated Na+uptake was obtained. The addition of 8‐bromo‐cyclic AMP (1 mM) had no effect on either DMPP‐ or veratridine‐stimulated Na+uptake. These observations suggest that D1‐selective agonists are inhibiting secretagogue‐stimulated Na+uptake in a cyclic AMP‐independent manner.