Grotmol T, Rødnes J T, Buanes T, Christensen G, Landsverk T
University of Oslo, Institute for Experimental Medical Research, Norway.
Acta Physiol Scand. 1993 Apr;147(4):417-29. doi: 10.1111/j.1748-1716.1993.tb09517.x.
The aim of this study was to test whether atrial natriuretic factor (ANF) exerts any effect on human intestinal ion transport, and the porcine intestine was used as a positive control of ANF's effects. Tissues from human proximal (n = 6) and distal (n = 6) colons, and from distal ileum (n = 6) were mounted in Ussing chambers, and short circuit current (Isc) was measured subsequent to serosal application of ANF (10(-6) M), 8-Br-cyclic guanosine monophosphate (8-Br-cGMP) (10(-4) M), and theophylline (10(-2) M). ANF did not affect Isc whereas 8-Br-cGMP increased Isc by 28 (8-53), 16 (3-36), and 16 (5-41) microA cm-2 in the distal colon (DC), proximal colon (PC) and distal ileum (DI), respectively. Likewise, transepithelial potential difference (PD) became more negative by 5.0 (0.6-8.9), 2.5 (0.4-4.0) and 0.9 (0.3-2.3) mV in DC, PC, and DI, respectively, subsequent to addition of 8-Br-cGMP. Isc and PD were further increased by theophylline. Additional radio-isotope flux studies in human colon revealed that ANF did not affect electroneutral sodium and chloride transport either. For comparison, ANF (10(-6) M) was administered to large intestinal tissues from young pigs in which ANF induced a significant increase in Isc which was comparable to the 8-Br-cGMP response in humans. The porcine Isc response was partly inhibited by chloride-free solution on the serosal side, by serosal application of bumetanide (10(-4) M) and BaCl2 (10(-3) M), and mucosal application of the chloride-channel blocker diphenylamine-2-carboxylate (DPC) (10(-3) M). Mucosal amiloride (10(-5) M) pre-treatment reduced baseline Isc but did not affect the porcine intestinal Isc response to ANF. In vitro radio-autography demonstrated specific binding sites for ANF in porcine distal colon, whereas no apparent labelling was observed in human distal colon. These findings suggest that the lack of effect of ANF on sodium and chloride transport in human distal ileum and colon is probably due to lack of ANF receptors. In the porcine intestine, however, the Isc response induced by ANF seems to involve stimulation of electrogenic chloride secretion, whereas electrogenic sodium absorption seems unaffected.
本研究的目的是测试心房利钠因子(ANF)是否对人体肠道离子转运有任何影响,并将猪肠道用作ANF作用的阳性对照。将来自人类近端结肠(n = 6)和远端结肠(n = 6)以及远端回肠(n = 6)的组织安装在尤斯灌流室中,在浆膜侧施用ANF(10⁻⁶ M)、8-溴环鸟苷单磷酸(8-Br-cGMP)(10⁻⁴ M)和茶碱(10⁻² M)后测量短路电流(Isc)。ANF对Isc没有影响,而8-Br-cGMP在远端结肠(DC)、近端结肠(PC)和远端回肠(DI)中分别使Isc增加了28(8 - 53)、16(3 - 36)和16(5 - 41)μA/cm²。同样,添加8-Br-cGMP后,DC、PC和DI中的跨上皮电位差(PD)分别更负5.0(0.6 - 8.9)、2.5(0.4 - 4.0)和0.9(0.3 - 2.3)mV。茶碱进一步增加了Isc和PD。在人体结肠中进行的额外放射性同位素通量研究表明,ANF对电中性钠和氯的转运也没有影响。为了进行比较,将ANF(10⁻⁶ M)施用于幼猪的大肠组织,其中ANF使Isc显著增加,这与人类对8-Br-cGMP的反应相当。猪的Isc反应部分受到浆膜侧无氯溶液、浆膜施用布美他尼(10⁻⁴ M)和氯化钡(10⁻³ M)以及黏膜施用氯通道阻滞剂二苯胺-2-羧酸盐(DPC)(10⁻³ M)的抑制。黏膜用氨氯地平(10⁻⁵ M)预处理可降低基线Isc,但不影响猪肠道对ANF的Isc反应。体外放射自显影显示猪远端结肠中有ANF的特异性结合位点,而在人类远端结肠中未观察到明显的标记。这些发现表明,ANF对人类远端回肠和结肠中钠和氯转运缺乏影响可能是由于缺乏ANF受体。然而,在猪肠道中,ANF诱导的Isc反应似乎涉及刺激电生性氯分泌,而电生性钠吸收似乎未受影响。