Cox H M, Cuthbert A W, Munday K A
Br J Pharmacol. 1987 Feb;90(2):393-401. doi: 10.1111/j.1476-5381.1987.tb08969.x.
Epithelial sheets from rat jejunum and descending colon have been shown to respond to angiotensin II (AII) when studied under short-circuit conditions and bathed on both sides with Krebs-Henseleit solution. The octapeptide AII elicited increases in short-circuit current (SCC) in preparations of jejunum and decreases in SCC in the descending colon; both responses occurred when the peptide was applied to the basolateral surface, but not when applied to the apical solution. Responses in both tissues were highly specific, being inhibited by a range of AII antagonists with the following order of potency: [Sar1. Thr8]-AII greater than [Sar1. Leu8]-AII greater than [Sar1. Ile8]-AII greater than [Sar1. Ala8]-AII greater than [Des,Asp1. Ile8]-AII in rat jejunum. AII responses were not affected by alpha- or beta- adrenoceptor antagonists, atropine or tetrodotoxin. AII responses were totally inhibited by the chloride channel blocker, diphenylamine-2-carboxylate (DPC) while cotransport inhibitors e.g. piretanide and frusemide significantly reduced the size of AII responses in colon and jejunum. These patterns of activity suggest that in the jejunum the responses result from electrogenic chloride secretion. Although AII responses in colon were sensitive to DPC the transporting ions have not yet been identified. Both piroxicam and indomethacin inhibited the increase in SCC elicited by AII in the jejunum, and the reduction in SCC caused by AII in the colon. Taken together these results indicate that eicosanoids are involved in AII responses in both tissues. This is the first study to demonstrate a direct, electrogenic effect for AII on transporting epithelia from the gastrointestinal tract. The responses are most probably initiated by All interacting with previously identified specific All receptors within the epithelial membranes.
在短路条件下，用Krebs-Henseleit溶液双侧灌流大鼠空肠和降结肠的上皮片时，已证明其对血管紧张素II（AII）有反应。八肽AII使空肠标本的短路电流（SCC）增加，而降结肠的SCC降低；当该肽应用于基底外侧表面时，两种反应均会出现，但应用于顶端溶液时则不会。两种组织中的反应都具有高度特异性，受到一系列AII拮抗剂的抑制，其效力顺序如下：在大鼠空肠中，[Sar1. Thr8]-AII大于[Sar1. Leu8]-AII大于[Sar1. Ile8]-AII大于[Sar1. Ala8]-AII大于[Des,Asp1. Ile8]-AII。AII反应不受α或β肾上腺素能受体拮抗剂、阿托品或河豚毒素的影响。AII反应被氯离子通道阻滞剂二苯胺-2-羧酸盐（DPC）完全抑制，而协同转运抑制剂（如吡咯他尼和呋塞米）显著降低了结肠和空肠中AII反应的幅度。这些活性模式表明，在空肠中，反应是由电致性氯离子分泌引起的。虽然结肠中的AII反应对DPC敏感，但转运离子尚未确定。吡罗昔康和吲哚美辛均抑制了AII引起的空肠SCC增加以及AII引起的结肠SCC降低。综合这些结果表明，类花生酸参与了两种组织中的AII反应。这是第一项证明AII对胃肠道转运上皮具有直接电致效应的研究。这些反应很可能是由AII与上皮膜内先前鉴定的特异性AII受体相互作用引发的。
