Adrenergic modulation of Escherichia coli O157:H7 adherence to the colonic mucosa

Benedict T. Green, Mark Lyte, Chunsheng Chen, Yonghong Xie, Melissa A. Casey, Anjali Kulkarni-Narla, Lucy Vulchanova, David R. Brown

Research output: Contribution to journalArticle

67 Scopus citations

Abstract

Enteric neurotransmitters can modulate the biodefensive functions of the intestinal mucosa, but their role in mucosal interactions with enteropathogens is not well defined. Here we tested the hypothesis that norepinephrine (NE) modulates interactions between enterohemorrhagic Escherichia coli O157:H7 (EHEC) and the colonic epithelium. Mucosal sheets from porcine distal colon were mounted in Ussing chambers. Drugs and an inoculum of either Shiga toxin-negative or -positive EHEC were added to the contraluminal and luminal bathing medium, respectively. After 90 min, adherent bacteria were quantified by an adherence assay and by immunohistochemical methods; short-circuit current (Isc) was measured continuously to assess changes in active ion transport. NE-treated tissues exhibited concentration-dependent increases in Isc and EHEC adherence. NE did not alter adherence of a rodent-adapted, noninfectious E. coli strain or two porcine-adapted non-O157 E. coli strains. The actions of NE on EHEC adherence but not Isc were prevented by the α-adrenergic antagonist yohimbine and the PKA activator Sp-8-bromoadenosine-3′, 5′-cyclic monophosphorothioate. Like NE, the PKA inhibitor Rp-8-bromoadenosine-3′,5′-cyclic monophosphorothioate or indirectly acting sympathomimetic agents increased EHEC adherence. Nerve fibers immunoreactive for the NE-synthesizing enzymes tyrosine hydroxylase and dopamine β-hydroxylase appeared to innervate the colonic epithelium. EHEC-like immunoreactivity on the colonic surface had the appearance of bacterial microcolonies and increased after NE treatment by a phentolamine-sensitive mechanism. Through interactions with α2-adrenergic receptors, NE appears to increase EHEC adherence to the colonic mucosa. Changes in sympathetic neural outflow may alter intestinal susceptibility to infection.

Original languageEnglish (US)
Pages (from-to)G1238-G1246
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume287
Issue number6 50-6
DOIs
StatePublished - Dec 1 2004

    Fingerprint

Keywords

  • Colonocyte
  • Enteritis
  • Protein kinase A
  • Sympathetic nervous system
  • α-adrenergic receptor

Cite this