Abstract
The aim of our study was to further investigatethe pathophysiological mechanism underlying idiopathicchronic constipation (ICC), a disorder of colonicmotility. A possible alteration of excitatory and inhibitory neurotransmission and also the roleof inhibitory neurotransmitters such as nitric oxide(NO), 5′-adenosine triphosphate (ATP), andvasoactive intestinal peptide (VIP) has been evaluatedon preparations of distal colon from patients with or withoutICC. The isometric tension was recorded from isolatedcircular muscle strips of both experimental groupsduring pharmacological and electrical field stimulation (EFS). The contractile response obtained byacetylcholine (ACh 20 μM), EFS (20 Hz, 20 V, 1 msec,pulse trains lasting 1 min) and substance P (SP 1 μM)was significantly lower in ICC than in controlpreparations. The effect of inhibitory nonadrenergic,noncholinergic innervation was evaluated using EFS atlow frequencies (0.5-8 Hz), after cholinergic andsympathetic blockade with atropine (3 μM) andguanethidine (3 μM). The maximum relaxation valueexpressed as percentage of inhibition of SP-inducedcontraction was significantly higher in ICC than incontrol preparations (87 ± 2.4 and 67 ±6.3, respectively; P < 0.05). Experiments with substances thatantagonize or reduce the effect of putative inhibitorymediators (VIP 6-28, apamin andNG-nitro-L-arginine) suggest that analteration in NO and ATP release is present in ICC preparations. In particularat a higher inhibitory frequency NO-mediated relaxationis enhanced in ICC vs control, supporting the hypothesisthat excessive NO production may be involved in pathophysiological mechanism ofconstipation.
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Mitolo-Chieppa, D., Mansi, G., Rinaldi, R. et al. Cholinergic Stimulation and Nonadrenergic, Noncholinergic Relaxation of Human Colonic Circular Muscle in Idiopathic Chronic Constipation. Dig Dis Sci 43, 2719–2726 (1998). https://doi.org/10.1023/A:1026615730533
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DOI: https://doi.org/10.1023/A:1026615730533