Thomson S, Bao D, Deng A, Vallon V
Department of Medicine, University of California San Diego and San Diego Veterans Affairs Medical Center, San Diego, California, USA.
J Clin Invest. 2000 Jul;106(2):289-98. doi: 10.1172/JCI8761.
Nephron function is stabilized by tubuloglomerular feedback (TGF). TGF operates within the juxtaglomerular apparatus, sensing changes in tubular flow and eliciting compensatory changes in single nephron GFR (SNGFR). The mediator(s) of TGF remains unconfirmed. One theory is that ATP consumed in active transport by the macula densa leads to formation of adenosine, which causes glomerular vasoconstriction. We performed micropuncture in rats to test this hypothesis. Adenosine activity was manipulated by microperfusing nephrons with adenosine A1 receptor blocker, A1-agonist, or 5'-nucleotidase inhibitor. Effects on TGF were characterized by changes in TGF efficiency (the compensation for small perturbations in tubular flow) and by changes in the maximum range over which TGF can cause SNGFR to change. These data were further applied to generate TGF profiles [SNGFR versus late proximal flow (V(LP))]. TGF efficiency was significantly reduced by blocking A1-receptors. TGF efficiency, TGF range, and the slope of the TGF profile (DeltaSNGFR/DeltaV(LP)) were all significantly reduced by blocking 5'-nucleotidase. When adenosine activity was clamped by combining 5'-nucleotidase inhibitor with A1-agonist to determine whether TGF requires adenosine to be present or to fluctuate, the TGF slope was reduced by 83%, indicating that adenosine activity must fluctuate for normal TGF to occur and that adenosine is a mediator of TGF.
肾小管-肾小球反馈（TGF）可稳定肾单位功能。TGF在肾小球旁器内发挥作用，感知肾小管液流变化并引发单个肾单位肾小球滤过率（SNGFR）的代偿性变化。TGF的介质尚未得到证实。一种理论认为，致密斑主动转运过程中消耗的ATP会导致腺苷形成，进而引起肾小球血管收缩。我们对大鼠进行了微穿刺实验以验证这一假说。通过向肾单位微灌注腺苷A1受体阻滞剂、A1激动剂或5'-核苷酸酶抑制剂来调控腺苷活性。通过TGF效率（对肾小管液流微小扰动的代偿）变化以及TGF能使SNGFR发生变化的最大范围变化来表征对TGF的影响。这些数据进一步用于生成TGF曲线[SNGFR与近端小管晚期液流（V(LP)）的关系]。阻断A1受体可显著降低TGF效率。阻断5'-核苷酸酶可使TGF效率、TGF范围以及TGF曲线斜率（ΔSNGFR/ΔV(LP)）均显著降低。当将5'-核苷酸酶抑制剂与A1激动剂联合使用以钳制腺苷活性，从而确定TGF是否需要腺苷存在或波动时，TGF斜率降低了83%，这表明腺苷活性必须波动才能发生正常的TGF，且腺苷是TGF的介质。
