Purinergic and nitrergic junction potential in the human colon.

The aim of the present work is to investigate a putative junction transmission [nitric oxide (NO) and ATP] in the human colon and to characterize the electrophysiological and mechanical responses that might explain different functions from both neurotransmitters. Muscle bath and microelectrode techniques were performed on human colonic circular muscle strips. The NO donor sodium nitroprusside (10 microM), but not the P2Y receptor agonist adenosine 5'-O-2-thiodiphosphate (10 microM), was able to cause a sustained relaxation. NG-nitro-L-arginine (L-NNA) (1 mM), a NO synthase inhibitor, but not 2'-deoxy-N6-methyl adenosine 3',5'-diphosphate tetraammonium salt (MRS 2179) (10 microM), a P2Y antagonist, increased spontaneous motility. Electrical field stimulation (EFS) at 1 Hz caused fast inhibitory junction potentials (fIJPs) and a relaxation sensitive to MRS 2179 (10 microM). EFS at higher frequencies (5 Hz) showed biphasic IJP with fast hyperpolarization sensitive to MRS 2179 followed by sustained hyperpolarization sensitive to L-NNA; both drugs were needed to fully block the EFS relaxation at 2 and 5 Hz. Two consecutive single pulses induced MRS 2179-sensitive fIJPs that showed a rundown. The rundown mechanism was not dependent on the degree of hyperpolarization and was present after incubation with L-NNA (1 mM), hexamethonium (100 microM), MRS 2179 (1 microM), and NF023 (10 microM). We concluded that single pulses elicit ATP release from enteric motor neurons that cause a fIJP and a transient relaxation that is difficult to maintain over time; also, NO is released at higher frequencies causing a sustained hyperpolarization and relaxation. These differences might be responsible for complementary mechanisms of relaxation being phasic (ATP) and tonic (NO).

Characterization of functional and morphological changes in a rat model of colitis induced by Trichinella spiralis.

We intended to characterize the effect of inflammation on the spontaneous colonic motility pattern and the role of iNOS in its disruption in colitis. Colitis was induced by an intracolonic enema of T. spiralis larvae. Animals were studied 2-30 days postinfection (PI). Standard H&E and iNOS staining was performed on colonic sections. Altered stool consistency was found from day 1 to day 21 PI; leukocytosis peaked on days 6-21 PI. Edema and cell infiltration were found in mucosa and submucosa (days 2-14 PI). Contractility displayed a disorganized pattern with decreased high-amplitude, low-frequency (HALF) contractions. A progressive fading of spontaneous activity was observed and was partly restored in strips devoid of submucosa. iNOS immunoreactivity increased in epithelial and infiltrating cells (days 2-14 PI). In this model of colonic inflammation, the decrease in spontaneous contractility, which might be caused by NO generated from mucosal and submucosal iNOS, bears some traits with changes observed in ulcerative colitis and might thus be useful to study the dismotility observed in this human disease.