Differential effects of UTP and ATP on ion transport in porcine tracheal epithelium
作者:S K Inglis、R E Olver、S M Wilson
DOI:10.1038/sj.bjp.0703324
日期:2000.5
Isolated segments of porcine tracheal epithelium were mounted in Ussing chambers, current required to maintain transepithelial potential difference at 0 mV (short circuit current, ISC) was monitored and effects of nucleotides upon ISC were studied.
Mucosal UTP (100 μM) evoked a transient rise in ISC that was followed by a sustained fall below basal ISC maintained for 30 min. Mucosal ATP (100 μM) also stimulated a transient rise in ISC but in contrast to UTP did not inhibit basal ISC. Submucosal UTP and ATP both transiently increased ISC.
UTP‐prestimulated epithelia were refractory to ATP but prestimulation with ATP did not abolish the response to UTP. The epithelia thus appear to express two populations of apical receptors allowing nucleotides to modulate ISC.
The UTP‐induced rise was reduced by pretreatment with either bumetanide (100 μM), diphenylamin‐2‐carboxylic acid (DPC, 1 mM), or Cl− and HCO3−‐free solution whilst the fall was abolished by amiloride pretreatment.
Thapsigargin (0.3 μM) abolished the UTP‐induced increase in ISC but not the subsequent decrease. Staurosporine (0.1 μM) inhibited basal ISC and blocked UTP‐induced inhibition of ISC. Inhibitors of either protein kinase C (PKC) (D‐erythro sphingosine) or PKA (H89) had no effect.
This study suggests that UTP stimulates Cl− secretion and inhibits basal Na+ absorption. ATP has a similar stimulatory effect, which may be mediated by activation of P2Y2 receptors and an increase in [Ca2+]in, but no inhibitory effect, which is likely mediated by activation of a pyrimidine receptor and possible inhibition of a protein kinase other than PKC or PKA.
British Journal of Pharmacology (2000) 130, 367–374; doi:10.1038/sj.bjp.0703324
以下是文本的中文翻译:
将猪气管上皮的分离段放置于尤金箱(Ussing chamber)中,监测维持跨上皮电位差为0 mV所需的电流(短路电流,ISC),并研究核苷酸对ISC的影响。
黏膜侧的UTP(100 μM)引发短暂的ISC上升,随后出现持续30分钟的基线ISC下降。黏膜侧的ATP(100 μM)同样刺激短暂的ISC上升,但与UTP不同,它并未抑制基线ISC。而基底侧的UTP和ATP均短暂增加ISC。
预刺激UTP的上皮对ATP无反应,但以ATP预刺激并不会消除对UTP的反应。这些结果表明,上皮细胞表面存在两组受体,使核苷酸能够调节ISC。
UTP诱导的上升被预先用布美他尼(100 μM)、二苯基氨基-2-羧酸(DPC,1 mM)或无Cl−和HCO3−的溶液处理所抑制,而下降则被预先用阿米洛利处理所消除。
Thapsigargin(0.3 μM)消除了UTP诱导的ISC增加,但未影响随后的下降。Staurosporine(0.1 μM)抑制基线ISC并阻断UTP诱导的ISC抑制。蛋白激酶C(PKC)抑制剂(D-赤藓醇基鞘氨醇)或蛋白激酶A(PKA)抑制剂(H89)均无作用。
本研究表明,UTP刺激Cl−分泌并抑制基线Na+吸收。ATP具有类似的刺激作用,可能是通过激活P2Y2受体和增加[Ca2+]in介导,但无抑制作用,这可能是通过激活嘧啶受体并可能抑制其他蛋白激酶(而非PKC或PKA)。
《英国药理学杂志》 (2000), 130, 367–374; doi:10.1038/sj.bjp.0703324