Nitric oxide mediates a therapeutic effect of nicotine in ulcerative colitis.
BACKGROUND
Ulcerative colitis is a condition of nonsmokers in which nicotine is of therapeutic benefit.


OBJECTIVE
To examine the in vitro effect of nicotine on colonic smooth muscle activity and the role of nitric oxide (NO) as a mediator.


METHODS
Nicotine, 1-10 microM, was administered to strips of circular muscle from the distal sigmoid colon of 9 patients with active ulcerative colitis and 18 with colorectal cancer. The effect of electrical field stimulation (EFS) was examined before nicotine was added. Finally L-NAME, a NO synthetase inhibitor, was added before nicotine was administered again.


RESULTS
Muscle strips developed similar spontaneous resting tone. In response to EFS, ulcerative colitis tissue developed lower tensions than the controls. Nicotine significantly reduced the resting tone and peak tension after EFS, with a greater effect in controls. With L-NAME, peak tensions were increased more in ulcerative colitis than controls, and nicotine produced a much smaller reduction.


CONCLUSIONS
Nicotine reduces circular muscle activity, predominantly through the release of nitric oxide-this appears to be 'up-regulated' in active ulcerative colitis. These findings may explain some of the therapeutic benefit from nicotine (and smoking) in ulcerative colitis and may account for the colonic motor dysfunction in active disease.
Green
J T
JT
Department of Gastroenterology, University Hospital of Wales, Cardiff, UK.
Richardson
C
C
Marshall
R W
RW
Rhodes
J
J
McKirdy
H C
HC
Thomas
G A
GA
Williams
G T
GT
D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D003082:Colectomy; D003093:Colitis, Ulcerative / Q000188:drug therapy* / Q000601:surgery; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D016166:Free Radical Scavengers / Q000494:pharmacology*; D005731:Ganglionic Stimulants / Q000037:antagonists & inhibitors / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009538:Nicotine / Q000037:antagonists & inhibitors / Q000627:therapeutic use*; D009569:Nitric Oxide / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects
D004791:Enzyme Inhibitors; D016166:Free Radical Scavengers; D005731:Ganglionic Stimulants; D009569:Nitric Oxide; D009538:Nicotine; D019331:NG-Nitroarginine Methyl Ester