Adrenocorticotrophic hormone modulates Escherichia coli O157:H7 adherence to porcine colonic mucosa

Exposure to stress is associated with susceptibility to disease and one stress mediator, norepinephrine, has been reported to enhance the adherence of enterohemorrhagic Escherichia coli O157:H7 (EHEC) to the colonic mucosa. We tested the hypothesis that adrenocorticotropic hormone (ACTH) and other stress-related hormones may act in a similar fashion. Explants of distal colonic mucosa from young pigs were mounted in Ussing chambers and their luminal aspect was exposed to EHEC strain 700728 for 30-90 min. When added to the contraluminal, but not luminal bathing medium, ACTH increased EHEC adherence within 90 min in a concentration-dependent manner (EC50 = 1.2 nM), but did not alter tissue electrical conductance. ACTH had no effect on the adherence of a pig-adapted non-O157 E. coli strain. The effect of 0.1 microM ACTH on luminal EHEC adherence was prevented in tissues pretreated contraluminally with the type 2 melanocortin receptor antagonist ACTH7-38, the neuronal conduction blocker saxitoxin, or the muscarinic cholinergic antagonist atropine. Moreover, ACTH7-38 decreased EHEC adherence in the absence of ACTH. These results suggest that ACTH acts via melanocortin receptors located on enteric nerves to enhance mucosal adherence of EHEC.