The dopamine receptor in adult and maturing kidney.
The dopamine receptor in adult and maturing kidney.
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DOI：
10.1152/ajprenal.1989.257.3.f315
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发表时间：
1989-09
期刊：
影响因子：
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通讯作者：
R. Felder;C. Felder;G. Eisner;Pedro A. Jose
中科院分区：
文献类型：
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作者：
R. Felder;C. Felder;G. Eisner;Pedro A. Jose
多巴胺和其他神经递质一样，通过占据特定的受体亚型发挥其生物学作用。中枢神经系统和某些内分泌器官中的多巴胺受体被分类为D1/D2亚型。在中枢神经系统之外，多巴胺受体被分类为DA 1/DA 2亚型。D1/D2和DA 1/DA 2受体具有显著的相似性和一些差异，其中最显著的是与D多巴胺受体相比，DA多巴胺的亲和力较低。DA 1受体激活增加肾血流量（RBF）; DA 1和DA 2受体的刺激也可能增加肾小球滤过率（GFR）。DA 1激动剂通过血流动力学机制间接抑制液体和电解质转运，并通过占据特定肾单位节段中的DA 1受体直接抑制液体和电解质转运。在近端小管中，DA 1激动剂刺激腺苷酸环化酶并抑制Na+-H+反向转运活性。它们还增加磷脂酶C并抑制Na+-K+-ATP酶活性（推测是蛋白激酶C活化的结果）。DA 2激动剂可促进后者的作用。在皮质集合管中，多巴胺拮抗盐皮质激素的作用和抗利尿激素的水肿作用。也有人认为，DA 1也可能通过影响其他激素（如心房利钠肽）来降低钠转运。由于多巴胺有刺激α-肾上腺素受体的倾向，所以对年轻人多巴胺的研究很复杂。多巴胺单独实际上可能会减少RBF在围产期。在一些动物中，多巴胺的肾血管舒张和利钠作用随着年龄的增长而增加。肾小管DA 1刺激的腺苷酸环化酶活性增加，而肾小管DA 1受体随着年龄的增长而减少。胎儿肾脏DA 2受体密度较大;出生后肾脏DA 2受体不发生变化。内源性多巴胺可能调节钠排泄在年轻人不同于成年人。在成年人中，钠过量与尿多巴胺的增加有关;年轻人则相反。多巴胺产生减少或多巴胺受体阻滞导致成人的抗钠尿;多巴胺阻滞导致年轻人的钠尿。这些与年龄相关的多巴胺效应差异是否是由于受体DA亚型密度、第二信使和/或与其他受体相互作用的变化，仍有待确定。
Dopamine, like other neurotransmitters, exerts its biological effects by occupation of specific receptor subtypes. The dopamine receptors in the central nervous system and certain endocrine organs are classified into the D1/D2 subtypes. Outside the central nervous system, the dopamine receptors are classified into the DA1/DA2 subtypes. The D1/D2 and DA1/DA2 receptor have marked similarities and some differences, the most notable of which is the lower affinity of the DA dopamine compared with the D dopamine receptor. DA1 receptor activation increases renal blood flow (RBF); stimulation of DA1 and DA2 receptors may also increase glomerular filtration rate (GFR). DA1 agonists inhibit fluid and electrolyte transport indirectly via hemodynamic mechanisms and directly by occupation of DA1 receptors in specific nephron segments. In the proximal tubule, DA1 agonists simulate adenylate cyclase and inhibit Na+-H+ antiport activity. They also increase phospholipase C and inhibit Na+-K+-ATPase activity (presumably as a consequence of protein kinase C activation). The latter effects may be facilitated by DA2 agonists. In cortical collecting ducts, dopamine antagonizes the effects of mineralocorticoids and the hydrosomotic effect of antidiuretic hormone. It has also been suggested that DA1 may also decrease sodium transport by influencing other hormones, such as atrial natriuretic peptide. Studies of dopamine in the young are complicated because of the propensity for dopamine to stimulate alpha-adrenoceptors. Dopamine alone may actually decrease RBF in the perinatal period. In some animals, the renal vasodilatory and natriuretic effects of dopamine increase with age. Renal tubular DA1-stimulated adenylate cyclase activity increases, whereas renal tubular DA1 receptors decrease with age. Renal DA2 receptor density is greater in the fetus; after birth renal DA2 receptors do not change. Endogenous dopamine may regulate sodium excretion in the young differently than in the adult. In the adult, sodium surfeit is associated with an increase in urinary dopamine; the opposite occurs in the young. A decrease in dopamine production or blockade of dopamine receptors results in an antinatriuresis in the adult; dopamine blockade in the young results in a natriuresis. It remains to be determined whether these age-related differences in dopamine effects are due to changes in receptor DA subtype density, second messengers, and/or interaction with other receptors.