Abnormal contractile properties of rectal smooth muscle in chronic ulcerative colitis.
BACKGROUND
Patients with ulcerative colitis have abnormal rectal motility.


OBJECTIVE
To compare the contractile properties of rectal smooth muscle from patients with ulcerative colitis and controls.


METHODS
Rectal smooth muscle strips from patients undergoing resection for ulcerative colitis or cancer (control) were mounted in an organ bath. The effects of carbachol (receptor-mediated) and potassium (causes membrane depolarization) were studied. Acetylcholinesterase histochemistry was performed and nerve counts compared.


RESULTS
Ulcerative colitis (n=41) and control (n=34) strips contracted in response to potassium and carbachol. Mean (S.E. M.) maximum response to potassium in the control and ulcerative colitis groups was 1.07 (0.06) g/mg and 1.02 (0.09) g/mg tissue, respectively (P=N.S.). EC50s (concentrations required to give 50% of maximal response) were 75 (1) mM and 73 (1) mM, respectively (P=N.S. ). Although maximum responses to carbachol were similar, 2.12 (0.12) g/mg and 1.95 (0.12) g/mg tissue (P=N.S.), ulcerative colitis strips exhibited an increased sensitivity to carbachol, EC50s: 5.05 x 10-6 (0.55 x 10-6) M vs. 8.36 x 10-6 (0.88 x 10-6) M, P=0.002). There was no significant difference in nerve counts between the tissues, as assessed by staining for acetylcholinesterase.


CONCLUSIONS
Ulcerative colitis tissue has an increased sensitivity to carbachol and this is not due to denervation; it may result from increased calcium release from intracellular stores since contraction due to membrane depolarization is not altered. Modulation of this pathway could potentially be used to alter rectal motility in patients with ulcerative colitis.
Cook
T A
TA
University Department of Pharmacology, John Radcliffe Hospital, Oxford, UK.
Brading
A F
AF
Mortensen
N J
NJ
D000110:Acetylcholinesterase / Q000378:metabolism; D002217:Carbachol / Q000494:pharmacology; D002452:Cell Count; D002908:Chronic Disease; D003093:Colitis, Ulcerative / Q000503:physiopathology*; D006651:Histocytochemistry; D006801:Humans; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000502:physiology; D009130:Muscle, Smooth / Q000294:innervation / Q000503:physiopathology*; D009197:Myenteric Plexus / Q000502:physiology; D018722:Nicotinic Agonists / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D012007:Rectum / Q000294:innervation / Q000503:physiopathology*
D018722:Nicotinic Agonists; D002217:Carbachol; D000110:Acetylcholinesterase; D011188:Potassium