A novel in vitro model of Brunner's gland secretion in the guinea pig duodenum

Abstract

A novel in vitro model that combined functional and morphological techniques was employed to directly examine pathways regulating Brunner's gland secretion in isolation from epithelium. In vitro submucosal preparations were dissected from guinea pig duodenum. A videomicroscopy technique was used to measure changes in luminal diameter of glandular acini as an index of activation of secretion. Carbachol elicited concentration-dependent dilations of the lumen (EC(50) = 2 microM) by activating muscarinic receptors on acinar cells. Ultrastructural and histological analyses demonstrated that dilation was accompanied by single and compound exocytosis of mucin-containing granules and the accumulation of mucoid material within the lumen. Inflammatory mediators (histamine, PGE(1), PGE(2)) and intestinal hormones (CCK, gastrin, vasoactive intestinal polypeptide, secretin) also stimulated glandular secretion, whereas activation of submucosal secretomotor neurons by 5-hydroxytryptamine did not. This study directly demonstrates that multiple hormonal, inflammatory, and neurocrine agents activate Brunner's glands, whereas many have dissimilar effects on the epithelium. This suggests that Brunner's glands are regulated by pathways that act both in parallel to and in isolation from those controlling epithelial secretion.

Munc18/SNARE proteins’ regulation of exocytosis in guinea pig duodenal Brunner’s gland acini

“…These results are very similar to our previous reports using video-microscopy real-time recording of the real time changes of dilatation of acini lumen to track secretion [1,6,7] . In those reports, we showed the range of cholinergic stimulation was between 0.1 μmol/L to 10 μmol/L, with EC50 of 2 μmol/L.…”

“…Brunner's gland acinar cells contain mucin granules in the apical cytoplasm and previous studies have shown that stimulation-evoked dilation of Brunner's gland apical lumen is associated with the deposition of mucin in this space [1] . In the current study, carbachol (1 μmol/L and 6 μmol/L) evoked a dose-dependent dilation of the lumen (Figure 1 A-C).…”

“…In vitro submucosal preparations containing Brunner's glands were dissected from the duodenum of guinea pigs (150-200 g) of either sex, as previously described [1,6,7] . Briefly, animals were anesthetized with isofluorane and killed by decapitation.…”

“…The Brunner's glands in the duodenum contribute to the discharge of mucin [1,2] and also the secretion of a number of other products, including immunoglobulin, lysozyme, epidermal growth factor, and trefoil peptides, which collectively contribute to mucosal protection [2][3][4][5] . Brunner's glands also secrete bicarbonate that contributes to the neutralization of the massive amount of acid coming from the stomach [2] , and duodenal alkalinization is critical for pancreatic enzyme survival.…”

A comparative histochemical study of the distribution of mucins in the gastrointestinal tracts of three insectivorous mammals

“…No acid mucins were observed in the stomach of C. cyanea. Emptying of the acidic stomach contents into the duodenum, along with gastric hydrochloric acid and proteases, creates a threat to the epithelial barrier of the duodenum (Moore et al, 2000). The secretion from Brunner's glands, along with pancreatic, bile and goblet cell secretions in the small intestine, neutralizes gastric hydrochloric acid (Takehana et al, 2000).…”