Effects of α2-adrenoceptor stimulation on luminal alkalinisation and net fluid flux in rat duodenum.

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 alkalinisa...

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Main Authors: Olof Nylander, Markus Sjöblom, John Sedin, David Dahlgren
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2022-01-01
Series:PLoS ONE
Online Access:https://doi.org/10.1371/journal.pone.0273208
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author Olof Nylander
Markus Sjöblom
John Sedin
David Dahlgren
author_facet Olof Nylander
Markus Sjöblom
John Sedin
David Dahlgren
author_sort Olof Nylander
collection DOAJ
description 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.
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spelling doaj.art-acc63e93c81345f4adbf2bbf8473eef62022-12-22T03:19:33ZengPublic Library of Science (PLoS)PLoS ONE1932-62032022-01-01178e027320810.1371/journal.pone.0273208Effects of α2-adrenoceptor stimulation on luminal alkalinisation and net fluid flux in rat duodenum.Olof NylanderMarkus SjöblomJohn SedinDavid DahlgrenThe 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.https://doi.org/10.1371/journal.pone.0273208
spellingShingle Olof Nylander
Markus Sjöblom
John Sedin
David Dahlgren
Effects of α2-adrenoceptor stimulation on luminal alkalinisation and net fluid flux in rat duodenum.
PLoS ONE
title Effects of α2-adrenoceptor stimulation on luminal alkalinisation and net fluid flux in rat duodenum.
title_full Effects of α2-adrenoceptor stimulation on luminal alkalinisation and net fluid flux in rat duodenum.
title_fullStr Effects of α2-adrenoceptor stimulation on luminal alkalinisation and net fluid flux in rat duodenum.
title_full_unstemmed Effects of α2-adrenoceptor stimulation on luminal alkalinisation and net fluid flux in rat duodenum.
title_short Effects of α2-adrenoceptor stimulation on luminal alkalinisation and net fluid flux in rat duodenum.
title_sort effects of α2 adrenoceptor stimulation on luminal alkalinisation and net fluid flux in rat duodenum
url https://doi.org/10.1371/journal.pone.0273208
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