Institute for Veterinary Physiology, University of Giessen, Giessen, Germany.
Biol Pharm Bull. 2011;34(6):789-93. doi: 10.1248/bpb.34.789.
Gaseous molecules such as nitric oxide (NO), hydrogen sulfide (H₂S), or carbon monoxide (CO) are involved in the regulation of colonic water and salt transport, which can be switched between absorption and secretion. Nitric oxide is produced from the amino acid L-arginine by different isoforms of the enzyme NO synthase, which are expressed both by enteric neurones and by the colonic epithelium. NO donors evoke a transepithelial Cl⁻ secretion in vitro. Most actions of NO are mediated by a stimulation of guanosine 5' cyclic monophosphate (cGMP) synthesis via activation of the soluble guanylate cyclase. In rat colon, NO possesses several main action sites: a stimulation of apical Cl⁻ channels most probably not related to cGMP-dependent phosphorylation, and an increase in the cytosolic Ca²⁺ concentration, which stimulates a Ca²⁺-dependent K⁺ conductance in the basolateral membrane. Hydrogen sulfide, produced during the metabolism of the amino acid L-cysteine, also evokes a Cl⁻ secretion, either by stimulation of secretomotor submucosal neurones as in guinea-pig colon or by activating Ca²⁺-dependent and ATP-sensitive K⁺ channels as in rat colon. The third gasotransmitter, CO, produced during the degradation of heme, evokes anion secretion carried by Cl⁻ and HCO₃⁻. This response is mainly caused by the activation of apical anion channels and a stimulation of Ca²⁺-dependent K⁺ channels via an increase of the cytosolic Ca²⁺ concentration. Consequently, gaseous molecules produced by enteric neurones, epithelial cells, as well-in the case of H₂S-the microbial flora affect key transport enzymes involved in colonic ion transport.
气态分子，如一氧化氮（NO）、硫化氢（H₂S）或一氧化碳（CO），参与调节结肠水和盐的转运，其可以在吸收和分泌之间切换。NO 由不同同工型的一氧化氮合酶（NOS）从氨基酸 L-精氨酸生成，NOS 既由肠神经元表达，也由结肠上皮细胞表达。NO 供体在体外引起跨上皮 Cl⁻分泌。NO 的大多数作用通过激活可溶性鸟苷酸环化酶来刺激鸟苷 5' 环单磷酸（cGMP）合成来介导。在大鼠结肠中，NO 具有几个主要作用部位：刺激顶端 Cl⁻通道，极有可能与 cGMP 依赖性磷酸化无关，以及增加细胞浆 Ca²⁺浓度，刺激基底外侧膜中的 Ca²⁺依赖性 K⁺电导。硫化氢由氨基酸 L-半胱氨酸代谢产生，也可通过刺激豚鼠结肠中的分泌运动性黏膜下神经元或激活大鼠结肠中的 Ca²⁺依赖性和 ATP 敏感性 K⁺通道来引起 Cl⁻分泌。第三种气体递质 CO 由血红素降解产生，可引起 Cl⁻和 HCO₃⁻的阴离子分泌。这种反应主要是通过激活顶端阴离子通道和通过增加细胞浆 Ca²⁺浓度来刺激 Ca²⁺依赖性 K⁺通道来引起的。因此，由肠神经元、上皮细胞产生的气态分子，以及在 H₂S 的情况下微生物菌群产生的气态分子，都会影响参与结肠离子转运的关键转运酶。
