Gastrin and D1 dopamine receptor interact to induce natriuresis and diuresis.
Gastrin and D1 dopamine receptor interact to induce natriuresis and diuresis.
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DOI：
10.1161/hypertensionaha.113.01094
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发表时间：
2013-11
期刊：
影响因子：
--
通讯作者：
Jose PA
中科院分区：
文献类型：
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作者：
Chen Y;Asico LD;Zheng S;Villar VA;He D;Zhou L;Zeng C;Jose PA
口服NaCl比静脉输注相同剂量的NaCl产生更大的尿钠和利尿作用。胃泌素是肾近端小管（RPT）细胞吸收的主要胃肠激素。我们假设肾胃泌素和多巴胺受体相互作用，协同增加钠排泄，其相互作用受损可能参与高血压的发病机制。在Wistar-Kyoto （WKY）大鼠中，输注胃泌素可诱导尿钠和利尿，在胃泌素（CCKBR; CI-988）或d1样受体拮抗剂（SCH23390）存在时，这种作用被消除。同样，非诺多巴（一种d1样受体激动剂）的利钠和利尿作用被SCH23390和CI-988阻断。然而，胃泌素和非诺多巴在自发性高血压大鼠（SHRs）中未观察到利钠作用。在RPT细胞中也证实了胃泌素/ d1样受体的相互作用。在WKY而非SHRs的RPT细胞中，刺激d1样受体或胃泌素受体均可抑制Na+-K+- atp酶活性，这种作用在SCH23390或CI-988存在时被阻断。在WKY和SHRs的RPT细胞中，CCKBR和D1受体（D1R）共免疫沉淀，D1R或CCKBR刺激WKY大鼠RPT细胞后，CCKBR和D1受体（D1R）均增加；一种受体的刺激增加了另一种受体的RPT细胞膜表达，这种效应在SHRs中没有观察到。这些数据表明CCKBR和d1样受体之间存在协同作用，以增加钠排泄。肾脏CCKBR与d1样受体（如D1R）之间的异常相互作用可能在高血压的发病机制中发挥作用。
Oral NaCl produces a greater natriuresis and diuresis than the intravenous infusion of the same amount of NaCl. Gastrin is the major gastrointestinal hormone taken up by renal proximal tubule (RPT) cells. We hypothesized that renal gastrin and dopamine receptors interact to synergistically increase sodium excretion, an impaired interaction of which may be involved in the pathogenesis of hypertension. In Wistar-Kyoto (WKY) rats, infusion of gastrin induced natriuresis and diuresis, which was abrogated in the presence of a gastrin (CCKBR; CI-988) or D1-like receptor antagonist (SCH23390). Similarly, the natriuretic and diuretic effects of fenoldopam, a D1-like receptor agonist, were blocked by SCH23390, as well as by CI-988. However, the natriuretic effects of gastrin and fenoldopam were not observed in spontaneously hypertensive rats (SHRs). The gastrin/D1-like receptor interaction was also confirmed in RPT cells. In RPT cells from WKY but not SHRs, stimulation of either D1-like or gastrin receptor inhibited Na+-K+-ATPase activity, an effect that was blocked in the presence of SCH23390 or CI-988. In RPT cells from WKY and SHRs, CCKBR and D1 receptor (D1R) co-immunoprecipitated, which was increased after stimulation of either D1R or CCKBR in RPT cells from WKY rats; stimulation of one receptor increased RPT cell membrane expression of the other receptor, effects that were not observed in SHRs. These data suggest that there is a synergism between CCKBR and D1-like receptors to increase sodium excretion. An aberrant interaction between the renal CCKBR and D1-like receptors (e.g., D1R) may play a role in the pathogenesis of hypertension.