The Impact of α-Adrenoceptors in the Regulation of the Hypotonicity-Induced Increase in Duodenal Mucosal Permeability In Vivo

• Published in: Pharmaceutics Vol. 13; no. 12; p. 2096
• Main Authors: Sedin, John, Dahlgren, David, Sjöblom, Markus, Nylander, Olof
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 06.12.2021; MDPI
• Subjects: Adrenergic receptors; alpha-adrenoceptor agonists; alpha-adrenoceptor antagonists; Animals; Blood pressure; clonidine; COX-2; Drug dosages; Effluents; Experiments; idazoxan; Laboratories; luminal osmolality; Motility; mucosal permeability; Nervous system; Permeability; phenylephrine; prazosin; Small intestine; yohimbine; α-adrenoceptor agonists; α-adrenoceptor antagonists; COX-2; idazoxan; phenylephrine; α-adrenoceptor agonists; clonidine; luminal osmolality; yohimbine; α-adrenoceptor antagonists; mucosal permeability; prazosin
• ISSN: 1999-4923; 1999-4923
• DOI: 10.3390/pharmaceutics13122096

The duodenal mucosa is regularly exposed to a low osmolality, and recent experiments suggest that hypotonicity increases mucosal permeability in an osmolality-dependent manner. The aim was to examine whether the sympathetic nervous system, via action on α-adrenoceptors, affects the hypotonicity-induced increase in duodenal mucosal permeability. The duodenum of anaesthetised rats was perfused in vivo with a 50 mM NaCl solution in the presence of adrenergic α-adrenoceptor drugs. Studied were the effects on mucosal permeability (blood-to-lumen clearance of Cr-EDTA), arterial blood pressure, luminal alkalinisation, transepithelial fluid flux, and motility. Hypotonicity induced a six-fold increase in mucosal permeability, a response that was reversible and repeatable. The α -adrenoceptor agonist clonidine abolished the hypotonicity-induced increase in mucosal permeability, reduced arterial blood pressure, inhibited duodenal motility, and decreased luminal alkalinisation. The α -adrenoceptor antagonists, yohimbine and idazoxan, prevented the inhibitory effect of clonidine on the hypotonicity-induced increase in mucosal permeability. The α -agonist phenylephrine or the α -antagonist prazosin elicited their predicted effect on blood pressure but did not affect the hypotonicity-induced increase in mucosal permeability. None of the α - or α -adrenoceptor drugs changed the hypotonicity-induced net fluid absorption. In conclusion, stimulation of the adrenergic α -adrenoceptor prevents the hypotonicity-induced increase in mucosal permeability, suggesting that the sympathetic nervous system has the capability to regulate duodenal mucosal permeability.