title: Removal of tonic nitrergic inhibition is a potent stimulus for human proximal colonic propagating sequences.
abstract: Propagating sequences (PS) are important in colonic propulsion and defecation, yet the triggers of these motor patterns are not understood. Nonadrenergic noncholinergic neurones are believed to modulate smooth muscle in the gastrointestinal tract via the ubiquitous inhibitory neurotransmitter nitric oxide (NO). In the mouse colon periods of quiescence correlate with an increase in the release of NO. We investigated the colonic response to NO synthase inhibition in the conscious human subject. Intravenous infusion of saline or N(G)-monomethyl-L-arginine (L-NMMA; 3 or 6 mg kg(-1) h(-1)) occurred in random order in six healthy volunteers in whom a 5 m long nasocolonic manometry catheter was positioned such that 16 recording sites, at 7.5-cm intervals, spanned the terminal ileum and colon. L-NMMA infusion at 3 mg kg(-1) h(-1), but not 6 mg kg(-1) h(-1) significantly (P = 0.02) increased proximal colonic PS frequency (2.0 +/- 1.9 vs 11.7 +/- 7.0 PS h(-1)) and non-propagating motor activity (5,296 +/- 2,750 vs 6,362 +/- 1,275 mmHg s). We conclude that blockade of NO synthesis has a stimulatory effect on the frequency of proximal colonic PS. This suggests removal of tonic nitrergic inhibition of the colon might be a physiological stimulus for propagating activity.
authors.affiliation: Department of Gastroenterology, The St George Hospital, University of New South Wales, Kogarah, NSW 2217, Australia.
authors.forename: P G
authors.initials: PG
authors.lastname: Dinning
authors.forename: M
authors.initials: M
authors.lastname: Szczesniak
authors.forename: I J
authors.initials: IJ
authors.lastname: Cook
mesh_terms: D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D003106:Colon / Q000502:physiology*; D003672:Defecation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007082:Ileum / Q000187:drug effects; D008297:Male; D008365:Manometry; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D019323:omega-N-Methylarginine / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase