Neural influences on human intestinal epithelium in vitro

Abstract

Key pointsr We present the first systematic and, up to now, most comprehensive evaluation of the basic features of epithelial functions, such as basal and nerve-evoked secretion, as well as tissue resistance, in over 2200 surgical specimens of human small and large intestine.r We found no evidence for impaired nerve-evoked epithelial secretion or tissue resistance with age or disease pathologies (stomach, pancreas or colon cancer, polyps, diverticulitis, stoma reversal). This indicates the validity of future studies on epithelial secretion or resistance that are based on data from a variety of surgical specimens.r ACh mainly mediated nerve-evoked and basal secretion in the small intestine, whereas vasoactive intestinal peptide and nitric oxide were the primary pro-secretory transmitters in the large intestine.r The results of the present study revealed novel insights into regional differences in nerve-mediated secretion in the human intestine and comprise the basis by which to more specifically target impaired epithelial functions in the diseased gut.Abstract Knowledge on basic features of epithelial functions in the human intestine is scarce. We used Ussing chamber techniques to record basal tissue resistance (R-basal) and short circuit currents (I SC; secretion) under basal conditions (I SC -basal) and after electrical field stimulation (I SC -EFS) of nerves in 2221 resectates from 435 patients. I SC -EFS was TTX-sensitive and of comparable magnitude in the small and large intestine. I SC -EFS or R-basal were not influenced by the patients' age, sex or disease pathologies (cancer, polyps, diverticulitis). Ion substitution, bumetanide or adenylate cyclase inhibition studies suggested that I SC -EFS depended on epithelial cAMP-driven chloride and bicarbonate secretion but not on amiloride-sensitive sodium absorption. Although atropine-sensitive cholinergic components prevailed for I SC -EFS of the duodenum, jejunum and ileum, PG97-269-sensitive [vasoactive intestinal peptide (VIP) receptor 1 antagonist] VIPergic together with L-NAME-sensitive nitrergic components dominated the I SC -EFS in colonic preparations. Differences in numbers of cholinergic or VIPergic neurons, sensitivity of epithelial muscarinic or VIP receptors, or stimulus frequency-dependent transmitter release were not responsible for the region-specific transmitter contribution to I SC -EFS. Instead, the low atropine-sensitivity of I SC -EFS in the colon was the result of high cholinesterase activity because neostigmine revealed cholinergic components. Colonic I SC -EFS remained unchanged after tachykinin, P2X, P2Y or A1 and A2 receptor blockade. R-basal was smaller and I SC -basal was higher in the small intestine. TTX and bumetanide decreased I SC -basal in all regions, suggesting nerve-dependent secretory tone. I SC -basal was atropine-sensitive in the small intestine and PG97-269-sensitive in the large intestine. This comprehensive study reveals novel insights into region-specific nerve-mediated secretion in the human small and large intestine.

Constipation-Predominant Irritable Bowel Syndrome Females Have Normal Colonic Barrier and Secretory Function

“…However, it is unclear if perfusion system based measurement of in vivo potential difference reflects mucosal secretory response or correlates with transit. A recent study using surgical specimens provided detailed description of baseline secretory and barrier properties of human intestinal mucosa-submucosa preparations from a variety of disease conditions except IBS [36]. Although baseline duodenal and colonic Isc values described were lower than ours, duodenal Isc was lower than rectosigmoid colonic Isc, similar to our observations.…”

Functional dyspepsia

“…Serotonin-induced duodenal ion secretion is reduced in functional dyspepsia 87 . Secretory activity, among others, is maintained by bicarbonate flux into the lumen 88 ; thus, the reduced ion secretion could indicate reduced bicarbonate secretion and, therefore, an impaired protection of the mucosa against high acid loads. Acute psychological stress can also increase duodenal mucosal permeability via mast cell activation mediated by corticotropin-releasing hormone 89 .…”

Peppermint and caraway oils have muscle inhibitory and pro‐secretory activity in the human intestine in vitro

“…This is particularly relevant for the in vivo situation because proper function of the gut requires that the neurally mediated peristaltic reflex is still operative. 11 Although we did not perform ion substitution experiments, we therefore conclude that peppermint and caraway evoked increases in short circuit current was mediated by luminal secretion of chloride and bicarbonate ions. 33 The discrepant results may be species-related but more likely are due to the high concentration (1-5 mg/mL) used in the rat study.…”

“…11 It seems that the gut uses these "opposing" actions to keep the content moist even in a quiescent intestine. However, this is exactly how ENS transmitters act under physiologic conditions.…”

“…10,11 Immediately after resection, samples were transferred by fast courier service to the laboratory under aseptic conditions in cold oxygenated sterile Krebs buffer. 10,11 Immediately after resection, samples were transferred by fast courier service to the laboratory under aseptic conditions in cold oxygenated sterile Krebs buffer.…”