Functional role of histamine receptors in the renal cortical collecting duct cells.
Functional role of histamine receptors in the renal cortical collecting duct cells.
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DOI：
10.1152/ajpcell.00420.2021
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发表时间：
2022-01
期刊：
影响因子：
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通讯作者：
A. Sudarikova;Mikhail V Fomin;Regina F. Sultanova;Ying Zhao;Samantha Perez;Mark Domondon;Margarita Shamatova;Daria V Lysikova;Denisha R. Spires;D. Ilatovskaya
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作者：
A. Sudarikova;Mikhail V Fomin;Regina F. Sultanova;Ying Zhao;Samantha Perez;Mark Domondon;Margarita Shamatova;Daria V Lysikova;Denisha R. Spires;D. Ilatovskaya
组胺是一种重要的免疫调节剂，也是过敏性炎症、胃酸分泌和神经传递的调节剂。尽管已报告肾脏中存在大量组胺水平，但尚未明确定义该化合物的肾脏病理学和生理学效应。本研究的目的是深入了解组胺相关通路在肾脏中的作用，重点是集合管（CD），这是肾单位的远端部分，对血压调节很重要。我们报告，所有四个组胺受体（HR）以及负责组胺代谢和合成的酶在培养的小鼠mpkCCDcl4细胞中表达，组胺引起这些细胞中细胞内Ca2+的剂量依赖性瞬时增加。此外，我们观察到剂量依赖性增加cAMP在CD细胞中组胺的反应。短路电流的研究，旨在测量Na+重吸收通过ENaC（上皮Na+通道）表明抑制ENaC介导的电流组胺孵育4小时后，和单通道膜片钳分析显示类似的ENaC开放概率之前和之后的急性组胺应用。在免疫细胞化学和qPCR中证实了对ENaC的长期（4 h）影响，表明组胺处理后αENaC的蛋白和基因表达降低。总之，我们的数据突出了CD细胞中HR的功能重要性，并提示组胺在炎症相关肾脏疾病中的潜在意义。需要进一步的研究来辨别HRs下游的分子途径，并评估特定受体在肾脏病理生理学中的作用。
Histamine is an important immunomodulator, as well as a regulator of allergic inflammation, gastric acid secretion, and neurotransmission. Although substantial histamine level has been reported in the kidney, renal pathological and physiological effects of this compound have not been clearly defined. The goal of this study was to provide insight into the role of histamine-related pathways in the kidney, with emphasis on the collecting duct (CD), a distal part of the nephron important for the regulation of blood pressure. We report that all four histamine receptors (HRs) as well as enzymes responsible for histamine metabolism and synthesis are expressed in cultured mouse mpkCCDcl4 cells, and histamine evokes a dose-dependent transient increase in intracellular Ca2+ in these cells. Furthermore, we observed a dose-dependent increase in cAMP in the CD cells in response to histamine. Short-circuit current studies aimed at measuring Na+ reabsorption via ENaC (epithelial Na+ channel) demonstrated inhibition of ENaC-mediated currents by histamine after a 4-hr incubation, and single-channel patch-clamp analysis revealed similar ENaC open probability before and after acute histamine application. The long-term (4 hr) effect on ENaC was corroborated in immunocytochemistry and qPCR, which showed a decrease in protein and gene expression for αENaC upon histamine treatment. In summary, our data highlight the functional importance of HRs in the CD cells and suggest potential implications of histamine in inflammation-related renal conditions. Further research is required to discern the molecular pathways downstream of HRs and assess the role of specific receptors in renal pathophysiology.