Luminal adenosine receptors regulate amiloride-sensitive Na+ channels in A6 distal nephron cells
Luminal adenosine receptors regulate amiloride-sensitive Na+ channels in A6 distal nephron cells
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DOI：
10.1152/ajprenal.1996.270.5.f798
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发表时间：
1996-05-01
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影响因子：
--
通讯作者：
Ling, BN
中科院分区：
文献类型：
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作者：
Ma, HP;Ling, BN
为了研究鲁米那腺苷对阿米洛利敏感性钠通道的影响，我们应用细胞贴附式膜片钳技术对A6远端肾单位细胞。暴露于管腔30 nM腺苷使通道数量X开放概率（NPo）从0.38 +/- 0.08增加至0.77 +/- 0.09（平均值+/- SE; P < 0.01，n = 17）。腔内暴露于A（1）受体拮抗剂（30 nM 8-环戊基-1，3-二丙基黄嘌呤）可消除（P = 0.17，n = 11），而A（1）激动剂（30 nM N-6-环己基腺苷）可再现（P < 0.02，n = 6）30 nM腺苷的刺激作用。相比之下，较高浓度的腔腺苷（1或10 μ M）使NPo分别从0.65 +/- 0.09降至0.24 +/- 0.10（P < 0.02，n = 11）和从0.80 +/- 0.11降至0.19 +/- 0.03（P < 0.01，n = 8）。A（2）拮抗剂（30 μ M 3，7-二甲基-1-炔丙基黄嘌呤; P = 0.2，n = 10）可消除高剂量鲁米那腺苷对通道的抑制作用，而A（2）激动剂（100 nM CGS-21680盐酸盐; P < 0.0005，n = 8）可模拟这种抑制作用。我们得出结论：1）远端肾单位Nai通道的嘌呤能调节是由刺激性顶端A（1）受体和抑制性顶端A（2）受体介导的; 2）基础尿腺苷浓度（nM）将刺激Na+重吸收，而较高的尿腺苷浓度（μ M），例如，肾缺血和滤过性NaCl负荷升高可增加Na+排泄; 3）尿腺苷可能参与远端肾单位Na+转运的反馈调节。
To investigate the effects of luminal adenosine on amiloride-sensitive Na+ channels, we applied the cell-attached patch-clamp technique to A6 distal nephron cells. Exposure to luminal 30 nM adenosine increased number of channels X open probability (NPo) from 0.38 +/- 0.08 to 0.77 +/- 0.09 (means +/- SE; P < 0.01, n = 17). Luminal exposure to an A(1)-receptor antagonist (30 nM 8-cyclo-pentyl-1,3-dipropylxanthine) abolished (P = 0.17, n = 11), whereas an A(1) agonist (30 nM N-6-cyclohexyladenosine) reproduced (P < 0.02, n = 6) the stimulatory effect of 30 nM adenosine. In contrast, higher concentrations of luminal adenosine (1 or 10 mu M) decreased NPo from 0.65 +/- 0.09 to 0.24 +/- 0.10 (P < 0.02, n = 11) and from 0.80 +/- 0.11 to 0.19 +/- 0.03 (P < 0.01, n = 8), respectively. Channel inhibition by high-dose luminal adenosine was abolished by an A(2) antagonist (30 mu M 3,7-dimethyl-1-propargylxanthine; P = 0.2, n = 10) and mimicked by an A(2) agonist (100 nM CGS-21680 hydrochloride; P < 0.0005, n = 8). We conclude that 1) purinergic regulation of distal nephron Nai channels is mediated by stimulatory apical A(1) receptors and inhibitory apical A(2) receptors; 2) basal urinary adenosine concentrations (in nM) would stimulate Na+ reabsorption, whereas higher urinary concentrations (in mu M), e.g., renal ischemia and elevations in filtered NaCl load, would increase Na+ excretion; and 3) urinary adenosine may be involved in feedback regulation of distal nephron Na+ transport.