Adenosine A2 receptors modulate tubuloglomerular feedback
Adenosine A2 receptors modulate tubuloglomerular feedback
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DOI：
10.1152/ajprenal.00211.2010
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发表时间：
2010-08-01
影响因子：
4.2
通讯作者：
Welch, William J.
中科院分区：
文献类型：
--
作者：
Carlstroem, Mattias;Wilcox, Christopher S.;Welch, William J.
首页--期刊主要分类--期刊细介绍--期刊题录与期刊详细文摘内容腺苷A(2)受体调节肾小管球反馈。Am J Physiol Renal Physiol 299：F412-F417,2010。2010年6月2日首次出版；DOI：10.1152/ajprenal.00211.2010。-腺苷可以通过激活传入小动脉上的A(1)受体来调节肾小管球球反应，但腺苷A(1)和A(2)受体都可以调节肾小球前阻力。我们验证了腺苷A(2)受体抵消A(1)受体的作用并调节转化生长因子的假设。用人工肾小管液(ATF)增加Henle环的灌注量(0~40nL/min)，以近端停流压(Delta P-SF)的变化作为最大转化生长因子的反应。血管紧张素转化生长因子单独或与A(2A)受体拮抗剂(ZM-241385；10(-7)或10(-5)摩尔/L)、A(1)受体拮抗剂(PSB-36；10(-8)摩尔/L)或A(1)(PSB-36；10(-8)摩尔/L)和A(2A)(ZM-241385；10(-7)摩尔/L)合用5min后观察最大转化生长因子反应。单独使用ATF的最大转化生长因子反应(Delta P-SF)为11.7+/-1.0毫米汞柱。特异性A(2)抑制(低剂量)增强转化生长因子的最大反应(15.7+/-0.8 mm Hg；P<；0.01)，而高剂量(非特异性抑制)则减弱这一反应(5.0+/-0.4 mm Hg；P<；0.001)。A(1)单独抑制可导致反常的转化生长因子反应，P-SF增加3.1+/-0.5毫米汞柱(P<；0.05)。同时应用A(1)和A(2)拮抗剂可消除转化生长因子的反应(P-SF：0.4+/-0.3毫米汞柱)。总而言之，腺苷A(2)受体通过抵消腺苷A(1)受体的作用来调节转化生长因子的反应。
Carlstrom M, Wilcox CS, Welch WJ. Adenosine A(2) receptors modulate tubuloglomerular feedback. Am J Physiol Renal Physiol 299: F412-F417, 2010. First published June 2, 2010; doi:10.1152/ajprenal.00211.2010.-Adenosine can mediate the tubuloglomerular (TGF) response via activation of A(1) receptors on the afferent arteriole, but both adenosine A(1) and A(2) receptors can regulate preglomerular resistance. We tested the hypothesis that adenosine A(2) receptors offset the effect of A(1) receptors and modulate the TGF. Maximal TGF responses were measured in male Sprague-Dawley rats as changes in proximal stop-flow pressure (Delta P-SF) in response to increased perfusion of the loop of Henle (0 to 40 nl/min) with artificial tubular fluid (ATF). The maximal TGF response was studied after 5 min of intratubular perfusion (10 nl/min) with ATF alone, or with ATF plus the A(2A) receptor antagonist (ZM-241385; 10(-7) or 10(-5) mol/l), A(1) receptor antagonist (PSB-36; 10(-8) mol/l), or with a combination of A(1) (PSB-36; 10(-8) mol/l) and A(2A) (ZM-241385; 10(-7) mol/l) antagonists. The maximal TGF response (Delta P-SF) with ATF alone was 11.7 +/- 1.0 mmHg. Specific A(2) inhibition (low dose) enhanced the maximal TGF response (15.7 +/- 0.8 mmHg; P < 0.01), whereas a high dose (unspecific inhibition) attenuated the response (5.0 +/- 0.4 mmHg; P < 0.001). A(1) inhibition alone led to a paradoxical TGF response, with an increase in P-SF of 3.1 +/- 0.5 mmHg (P < 0.05). Simultaneous application of A(1) and A(2) antagonists abolished the TGF response (Delta P-SF: 0.4 +/- 0.3 mmHg). In conclusion, adenosine A(2) receptors modulate the TGF response by counteracting the effects of adenosine A(1) receptors.