Differential regulation of renal phospholipase C isoforms by catecholamines.
Differential regulation of renal phospholipase C isoforms by catecholamines.
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DOI：
10.1172/jci117656
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发表时间：
1995
期刊：
影响因子：
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通讯作者：
Pei-Yung Yu;L. Asico;G. Eisner;P. Jose
中科院分区：
文献类型：
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作者：
Pei-Yung Yu;L. Asico;G. Eisner;P. Jose
多巴胺、D1激动剂和NE均能增加磷脂酰肌醇特异性磷脂酶C （PLC）的活性，但多巴胺产生尿钠作用，NE具有抗尿钠作用。为了确定儿茶酚胺是否对PLC异构体的表达有差异调节，我们在麻醉大鼠的肾动脉中静脉注射非诺多巴泮（D1激动剂）或普拉克索（D1/D2激动剂）或非诺多巴泮或NE。输注3-4小时后，当预期的尿钠（非诺多巴或普拉克索）或抗尿钠（NE）发生时，取出肾脏，分析PLC异构体蛋白表达活性。Western blot分析显示，在肾皮质膜中，非诺多巴泮和普拉克索增加了PLC β 1的表达，降低了PLC γ 1的表达；PLC delta不变。在细胞质中，普拉克索和非诺多巴增加了PLC β 1和PLC γ 1的表达。髓质未见影响。一种优先的D1拮抗剂SKF 83742本身没有作用，但它阻断了普拉克索的作用，从而证实了D1受体的参与。相反，NE也增加了PLC β 1，但不影响膜中PLC γ 1蛋白的表达。PLC异构体表达的变化伴随着PLC异构体活性的类似变化。这些研究首次证明了儿茶酚胺对PLC异构体的差异调节。
Dopamine and D1 agonists and NE all increase phosphatidyl inositol-specific phospholipase C (PLC) activity, but whereas dopamine produces a natriuresis, NE has an antinatriuretic effect. To determine if catecholamines differentially regulate the expression of PLC isoforms, we infused fenoldopam, a D1 agonist, or pramipexole, a D1/D2 agonist, intravenously or infused fenoldopam or NE into the renal artery of anesthetized rats. After 3-4 h of infusion, when the expected natriuresis (fenoldopam or pramipexole) or antinatriuresis (NE) occurred, the kidneys were removed for analysis of PLC isoform protein expression activity. Western blot analysis revealed that in renal cortical membranes, fenoldopam and pramipexole increased expression of PLC beta 1 and decreased expression of PLC gamma 1; PLC delta was unchanged. In the cytosol, pramipexole and fenoldopam increased expression of both PLC beta 1 and PLC gamma 1. No effects were noted in the medulla. A preferential D1 antagonist, SKF 83742, which by itself had no effect, blocked the effects of pramipexole, thus confirming the involvement of the D1 receptor. In contrast, NE also increased PLC beta 1 but did not affect PLC gamma 1 protein expression in membranes. The changes in PLC isoform expression were accompanied by similar changes in PLC isoform activity. These studies demonstrate for the first time differential regulation of PLC isoforms by catecholamines.