Holtug K, Hansen M B, Skadhauge E
Dept. of Medicine A, Rigshospitalet, University of Copenhagen, Denmark.
Scand J Gastroenterol Suppl. 1996;216:95-110. doi: 10.3109/00365529609094565.
A major advance in transport physiology was H. H. Ussing's development of the voltage-clamp method, and later the Koefoed-Johnsen-Ussing model for Na+ transport. In the same decade, J. C. Skou identified the Na(+)-K(+)-ATPase, which maintains the Na+ and K+ gradients that drive most epithelial transport processes. With this foundation, Danish scientists have pursued the mechanism of ion transport and the resulting solute-linked water flow. Recent contributions have been on isosmotic transport, suggesting solute recycling, and KCl-water cotransport in the basolateral epithelial cell membrane. Efficient small intestinal nutrient absorption is dependent on coupling to the Na+ gradient. Cotransport of Na+ and glucose is quantitatively the most important absorptive mechanism in the small intestine, as illustrated by the success of oral rehydration solutions in diarrhoea. The majority of amino acids are likewise transported by Na+ dependent carriers, but recent experiments have identified a concomitant Cl- dependency for some. Regulation of intestinal secretion, both under normal digestive processes, and in response to enterotoxins, has turned out to be very complex. It involves local and central neuronal regulation through an array of neurotransmitters and local actions of gastrointestinal hormones. Major effectors are the submucosal neurons and the main transmitters serotonin, vasoactive intestinal peptide, acetylcholine, substance P, and neurotensin. Development of antisecretagogues is impeded by the existence of several receptor subtypes and significant species differences. The Na+ and water-conserving properties of the large intestine have been shown to be regulated by adrenocortical hormones, with aldosterone as a potent stimulator of colonic Na+ absorption. A major colonic function is the symbiosis with the anaerobic bacterial population. The fermentation of carbohydrate to short-chain fatty acids, which can be absorbed, supplements small intestinal digestive function.
运输生理学的一项重大进展是H. H. 乌斯廷开发的电压钳方法，以及后来的科弗德 - 约翰森 - 乌斯廷钠转运模型。在同一十年中，J. C. 斯科发现了钠钾ATP酶，它维持着驱动大多数上皮运输过程的钠和钾梯度。在此基础上，丹麦科学家们深入研究了离子运输机制以及由此产生的溶质相关水流。近期的研究成果集中在等渗运输，提示溶质循环，以及基底外侧上皮细胞膜中的氯化钾 - 水共转运。高效的小肠营养吸收依赖于与钠梯度的耦合。钠和葡萄糖的共转运在数量上是小肠中最重要的吸收机制，口服补液溶液在腹泻治疗中的成功就证明了这一点。大多数氨基酸同样通过依赖钠的载体进行运输，但最近的实验发现其中一些还伴随着对氯的依赖性。事实证明，无论是在正常消化过程中还是对肠毒素的反应中，肠道分泌的调节都非常复杂。它涉及通过一系列神经递质进行的局部和中枢神经调节以及胃肠激素的局部作用。主要效应器是黏膜下神经元以及主要递质5-羟色胺、血管活性肠肽、乙酰胆碱、P物质和神经降压素。由于存在多种受体亚型和显著的物种差异，抗分泌剂的研发受到阻碍。大肠的保钠和保水特性已被证明受肾上腺皮质激素调节，醛固酮是结肠钠吸收的有效刺激剂。大肠的一项主要功能是与厌氧细菌群体共生。碳水化合物发酵产生可吸收的短链脂肪酸，补充了小肠的消化功能。
