Eto B, Boisset M, Griesmar B, Desjeux J F
Conservatoire National des Arts et Métiers, Laboratoire de Biologie, 75141 Paris 03, France.
Am J Physiol. 1999 Jan;276(1):G107-14. doi: 10.1152/ajpgi.1999.276.1.G107.
Stimulating water absorption in the colon represents an important target to reduce stool output in secretory diarrhea. Recently, a 153-amino-acid peptide was isolated from porcine upper small intestine and purified, taking into account the increase of water absorption in guinea pig gallbladder. Accordingly, this peptide was named sorbin. The aim of the present study was to determine if the COOH-terminal heptapeptide of sorbin (C7-sorbin) participates in the regulation of electrolyte transport in the colon. Different regions (from duodenum to colon) of stripped intestinal mucosa from rats or humans were mounted in Ussing chambers to measure the changes in short-circuit current (DeltaIsc) and net 22Na and 36Cl fluxes (JNanet and JClnet) after serosal exposure of 10(-7) to 10(-3) M C7-sorbin. In fasted rat intestine, C7-sorbin (10(-4) M) induced an immediate reduction in Isc in the distal ileum and proximal and distal colon but not in the duodenum and jejunum. In the colon, Isc reduction and JNanet and JClnet stimulation were dose dependent (EC50 = 2 x 10(-5) M). At 10(-3) M, maximal effect was observed (DeltaIsc = -1.14 +/- 0.05, DeltaJNanet = +4.97 +/- 1.38, and DeltaJClnet = +9.25 +/- 1.44 microeq. h-1. cm-2). C7-sorbin (10(-3) M) inhibited the increase in Isc induced by a series of 10 secretory agents such as secretin, vasoactive intestinal peptide, PGE2, and serotonin. In HT-29-Cl19A cells, C7-sorbin induced an increase in Isc, with a maximal effect at 10(-3) M (DeltaIsc = 0.29 +/- 0.10 microeq. h-1. cm-2). In human intestine, a dose-dependent decrease in Isc was observed in right and sigmoid colons in basal and stimulated conditions (EC50 congruent with 10(-5) M; at 10(-4) M, DeltaIsc = -2.66 +/- 0.17 microeq. h-1. cm-2) but not in the jejunum. The results indicate that C7-sorbin stimulated NaCl neutral absorption and inhibited electrogenic Cl- in rat and human intestinal epithelia. In addition, the antisecretory effect was essentially observed in the distal part of both rat and human intestine and the magnitude of the proabsorptive effect was directly related to the magnitude of the previously induced secretion.
刺激结肠对水的吸收是减少分泌性腹泻粪便量的一个重要靶点。最近，考虑到豚鼠胆囊中水吸收的增加，从猪的上段小肠中分离并纯化出一种153个氨基酸的肽。因此，这种肽被命名为索宾。本研究的目的是确定索宾的COOH末端七肽（C7 - 索宾）是否参与结肠中电解质转运的调节。将大鼠或人类剥离的肠黏膜不同区域（从十二指肠到结肠）安装在尤斯灌流小室中，以测量在浆膜侧暴露10⁻⁷至10⁻³ M C7 - 索宾后短路电流（ΔIsc）以及净²²Na和³⁶Cl通量（JNanet和JClnet）的变化。在禁食大鼠的肠道中，C7 - 索宾（10⁻⁴ M）可使回肠远端以及结肠近端和远端的Isc立即降低，但十二指肠和空肠则无此现象。在结肠中，Isc降低以及JNanet和JClnet的刺激呈剂量依赖性（半数有效浓度 = 2×10⁻⁵ M）。在10⁻³ M时，观察到最大效应（ΔIsc = -1.14 ± 0.05，ΔJNanet = +4.97 ± 1.38，ΔJClnet = +9.25 ± 1.44微当量·小时⁻¹·厘米⁻²）。C7 - 索宾（10⁻³ M）可抑制一系列10种分泌因子（如促胰液素、血管活性肠肽、前列腺素E2和5 - 羟色胺）诱导的Isc增加。在HT - 29 - Cl19A细胞中，C7 - 索宾可诱导Isc增加，在10⁻³ M时达到最大效应（ΔIsc = 0.29 ± 0.10微当量·小时⁻¹·厘米⁻²）。在人类肠道中，在基础状态和刺激状态下，右半结肠和乙状结肠的Isc呈剂量依赖性降低（半数有效浓度约为10⁻⁵ M；在10⁻⁴ M时，ΔIsc = -2.66 ± 0.17微当量·小时⁻¹·厘米⁻²），但空肠无此现象。结果表明，C7 - 索宾可刺激大鼠和人类肠上皮细胞对NaCl的中性吸收并抑制电生性Cl⁻分泌。此外，抗分泌作用主要在大鼠和人类肠道的远端观察到，且促吸收作用的大小与先前诱导的分泌大小直接相关。
