Neural influences on human intestinal epithelium in vitro

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) receptor1 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.