O Nylander1, M Sjöblom. 1. Department of Neuroscience, Division of Physiology, Biomedical Center, Uppsala University, Uppsala, Sweden. olof.nylander@fysiologi.uu.se
Abstract
AIMS: To examine whether modulation of paracellular solute permeability affects the capability of the duodenum to adjust luminal osmolality. METHODS: Proximal duodenum was perfused with a hypotonic NaCl solution and effects on paracellular permeability to (51)Cr-EDTA, motility, anion secretion, net fluid flux and perfusate osmolality determined in anaesthetized rats in the absence and presence of the COX-2 inhibitor parecoxib. Vasoactive intestinal peptide (VIP) was used to reduce and lidocaine to augment the hypotonicity-induced increase in paracellular permeability. RESULTS: Luminal hypotonicity slightly increased paracellular permeability in control animals. Parecoxib induced motility, increased electrolyte and fluid secretion, potentiated the hypotonicity-induced rise in paracellular permeability and enhanced the capability to adjust luminal osmolality. VIP, given to control animals stimulated electrolyte and fluid secretion and augmented the capability to adjust luminal osmolality. Administration of VIP to parecoxib-treated animals increased secretion further, markedly reduced the hypotonicity-induced increase in permeability but did not change the osmolality-adjusting capability. Luminal lidocaine potentiated the hypotonicity-induced increase in permeability, reduced the hypotonicity-induced net fluid absorption and the osmolality-adjusting capability was 50% greater than in controls. Lidocaine, given to parecoxib-treated animals potentiated the hypotonicity-induced increase in permeability, reduced the hypotonicity-induced net fluid absorption but did not change the osmolality-adjusting capability. CONCLUSIONS: Vasoactive intestinal peptide reduces the osmolality-adjusting capacity of the duodenum by inhibiting paracellular solute permeability but improves this capacity by stimulating active electrolyte and fluid secretion. In contrast, lidocaine improves the osmolality-adjusting capability by augmenting paracellular solute transport but depresses it by reducing the hypotonicity-induced net fluid absorption.
AIMS: To examine whether modulation of paracellular solute permeability affects the capability of the duodenum to adjust luminal osmolality. METHODS: Proximal duodenum was perfused with a hypotonicNaCl solution and effects on paracellular permeability to (51)Cr-EDTA, motility, anion secretion, net fluid flux and perfusate osmolality determined in anaesthetized rats in the absence and presence of the COX-2 inhibitor parecoxib. Vasoactive intestinal peptide (VIP) was used to reduce and lidocaine to augment the hypotonicity-induced increase in paracellular permeability. RESULTS:Luminal hypotonicity slightly increased paracellular permeability in control animals. Parecoxib induced motility, increased electrolyte and fluid secretion, potentiated the hypotonicity-induced rise in paracellular permeability and enhanced the capability to adjust luminal osmolality. VIP, given to control animals stimulated electrolyte and fluid secretion and augmented the capability to adjust luminal osmolality. Administration of VIP to parecoxib-treated animals increased secretion further, markedly reduced the hypotonicity-induced increase in permeability but did not change the osmolality-adjusting capability. Luminal lidocaine potentiated the hypotonicity-induced increase in permeability, reduced the hypotonicity-induced net fluid absorption and the osmolality-adjusting capability was 50% greater than in controls. Lidocaine, given to parecoxib-treated animals potentiated the hypotonicity-induced increase in permeability, reduced the hypotonicity-induced net fluid absorption but did not change the osmolality-adjusting capability. CONCLUSIONS: Vasoactive intestinal peptide reduces the osmolality-adjusting capacity of the duodenum by inhibiting paracellular solute permeability but improves this capacity by stimulating active electrolyte and fluid secretion. In contrast, lidocaine improves the osmolality-adjusting capability by augmenting paracellular solute transport but depresses it by reducing the hypotonicity-induced net fluid absorption.
Authors: David Dahlgren; Tobias Olander; Markus Sjöblom; Mikael Hedeland; Hans Lennernäs Journal: Acta Pharm Sin B Date: 2021-01-05 Impact factor: 11.413