Division of Physiology, Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden.
PLoS One. 2022 Aug 25;17(8):e0273208. doi: 10.1371/journal.pone.0273208. eCollection 2022.
The sympathetic nervous system is highly involved in the regulation of gastrointestinal functions such as luminal alkalinisation and fluid absorption. However, the exact mechanisms are not clear. This study aimed to delineate how α2-adrenergic receptor stimulation reduces duodenal luminal alkalinisation and induces net fluid absorption. This was tested by perfusing the duodenum of anesthetized rats with isotonic solutions devoid of Cl- and/or Na+, in the absence and presence of the α2-adrenoceptor agonist clonidine. The clonidine was also studied in rats treated with dimethylamiloride (a Na+/H+ exchange inhibitor), vasoactive intestinal peptide, and the nicotinic receptor antagonist hexamethonium. Clonidine reduced luminal alkalinisation and induced net fluid absorption. The Cl--free solution decreased luminal alkalinisation and abolished net fluid absorption, but did not prevent clonidine from doing so. Both the Na+-free solution and luminal dimethylamiloride increased luminal alkalinisation and abolished net fluid absorption, effects counteracted by clonidine. The NaCl-free solution (D-mannitol) did not affect luminal alkalinisation, but reduced net fluid absorption. Clonidine reduced luminal alkalinisation and induced net fluid absorption in rats perfused luminally with mannitol. However, clonidine did not affect the vasoactive intestinal peptide-induced increase in luminal alkalinisation or fluid secretion. Pre-treatment with hexamethonium abolished the effects of clonidine on luminal alkalinisation and net fluid flux. In summary, our in vivo experiments showed that clonidine-induced reduction in luminal alkalinisation and induction of net fluid absorption was unrelated to luminal Na+ and Cl-, or to apical Na+/H+ or Cl-/HCO3- exchangers. Instead, clonidine seems to exert its effects via suppression of nicotinic receptor-activated acetylcholine secretomotor neurons.
交感神经系统高度参与胃肠道功能的调节，如腔道碱化和液体吸收。然而，确切的机制尚不清楚。本研究旨在阐明α2-肾上腺素能受体刺激如何减少十二指肠腔道碱化并诱导净液体吸收。这是通过在没有和存在α2-肾上腺素受体激动剂可乐定的情况下，用不含 Cl-和/或 Na+的等渗溶液灌注麻醉大鼠的十二指肠来测试的。还在使用二甲氨乙酰胺（Na+/H+交换抑制剂）、血管活性肠肽和烟碱受体拮抗剂六烃季铵处理的大鼠中研究了可乐定。可乐定减少腔道碱化并诱导净液体吸收。无 Cl-溶液降低腔道碱化并消除净液体吸收，但不能阻止可乐定这样做。无 Na+溶液和腔内二甲氨乙酰胺均增加腔道碱化并消除净液体吸收，可乐定可拮抗这些作用。无 NaCl 溶液（甘露醇）不影响腔道碱化，但减少净液体吸收。可乐定减少甘露醇灌注大鼠的腔道碱化并诱导净液体吸收。然而，可乐定不影响血管活性肠肽诱导的腔道碱化或液体分泌增加。六烃季铵预处理消除了可乐定对腔道碱化和净液体通量的影响。总之，我们的体内实验表明，可乐定诱导的腔道碱化减少和净液体吸收诱导与腔道 Na+和 Cl-或顶端 Na+/H+或 Cl-/HCO3-交换器无关。相反，可乐定似乎通过抑制烟碱受体激活的乙酰胆碱分泌运动神经元发挥其作用。
