Background-In animals, activation of 5-HT 1 like receptors causes a relaxation of the gastric fundus through the activation of intrinsic inhibitory neurones. Aims-To investigate the eVect of sumatriptan, an agonist at enteric neuronal 5-HT 1 receptors, on fasting fundus tone and sensitivity to gastric distension in man. Methods-A gastric barostat was used to study the eVect of placebo and sumatriptan, 6 mg subcutaneously, on basal fundic tone in healthy subjects. In addition, stepwise isobaric and isovolumetric gastric distensions were performed and perception was measured before and after the administration of placebo and sumatriptan. Results-Placebo had no significant effects on gastric tone and on perception. Sumatriptan induced an immediate relaxation of the gastric fundus, reflected by an intragastric volume increase of 209 (39) ml (p<0.0005). After sumatriptan, intragastric pressures at the thresholds for perception or discomfort were not significantly altered. However, the intragastric volumes and the corresponding calculated wall tensions at perception and discomfort thresholds were significantly increased. Conclusions-Administration of the 5-HT 1 receptor agonist sumatriptan induces a relaxation of the gastric fundus in man, allowing larger intragastric volumes before thresholds for perception or discomfort are reached. The eVects of sumatriptan on the gastric fundus may have therapeutic potential in the treatment of patients with functional dyspepsia. (Gut 2000;46:468-473)

Fasting gastric fundus tone is maintained by continuous cholinergic input. 5-Hydroxytryptamine-1 (5-HT1) receptor activation decreases gastric fundus tone in humans. Whether this fundus-relaxing effect is mediated via inhibition of cholinergic input or via activation of a nitrergic pathway is unknown. The aim of the present study was to determine the effect of nitrergic inhibition on feline gastric fundus tone and on 5-HT1receptor-mediated relaxation of the fundus. Administration of N ω-nitro-l-arginine methyl ester (l-NAME) alone caused a significant decrease of the mean baseline volume ( P < 0.005), which was restored completely by addition ofl-arginine. Sumatriptan caused a dose-dependent relaxation of the gastric fundus ( P < 0.0005). This relaxation was inhibited by l-NAME ( P < 0.02) and was restored by prior administration of l-arginine. Buspirone did not cause any change in mean baseline volume, whereas the sumatriptan-induced relaxation was not affected by prior administration of NAN-190. Our data indicate that fasting fundus tone relies not only on continuous cholinergic input but also on continuous nitrergic input, implying that fasting fundus tone is maintained by the balance of a cholinergic and nitrergic drive. Furthermore, fundus relaxation via 5-HT1 receptor activation is mediated through activation of a nitrergic pathway.

Background-Previousstudies have failed to identify manometric patterns of gastrointestinal motor activity that can distinguish dyspepsia from health. Aims-To test the hypothesis that the combined use of prolonged, ambulatory, antrojejunal manometry and computer aided analysis in patients selected for the severity of their symptoms could reveal new insights into gastrointestinal motor activity in patients with severe motilitylike dyspesia Methods-Twenty four hour antrojejunal ambulatory manometry was performed in 14 patients and 10 healthy volunteers. Parameters characterising digestive and fasted motility were obtained by a validated computer program and visual analysis. Scoring systems quantified the degree of dysmotility as well as the severity of symptoms. Gastric emptying times were measured in each patient. Results-There was a high prevalence of antral and jejunal dysmotility both during the interdigestive period (71% of patients) and in the postprandial period (78%). During the interdigestive period there was a reduced incidence of antral and jejunal phases, a larger contribution of phase 2 during migrating motor complex cycles, and aberrant configuration of jejunal phase 3 in 29% of patients. Postprandially, the most frequent finding was antral (29% of patients) or jejunal (29%) hypomotility or hypermotility. Minute rhythm was present both during the postprandial (29% of patients) and the interdigestive period (21%). There was no positive correlation between symptom scores, gastric half emptying times, or motility scores. Conclusion-Even with the use of prolonged recordings and advanced computer aided analysis, it is not possible to identify a specific motor pattern which can discriminate patients with severe motility-like dyspepsia from those with other diseases or even healthy individuals. Clinical symptoms or gastric half emptying times are poor predictors of gastrointestinal dysmotility in patients with functional dyspepsia. (Gut 1998;42:235-242)

An algorithm has been developed for the offline analysis of prolonged manometric recordings in the upper small intestine of humans. Sample data are acquired in the human duodenum and jejunum six solid-state strain-gauge transducers mounted on a silicon catheter that is connected to a portable digital recording device. The data are sampled at 4 Hz and filtered. For accurate calculations, the filtered signals are converted to cubic B-spline functions of order four. Based on an exponential weighted moving average, a base-line is calculated from the signal. Contractions are recognised on the basis of thresholds for minimum amplitude and duration. The developed algorithm calculates properties of these contractions, such as amplitude, duration, area and a motility index. In addition, the program automatically recognises normal motor patterns of the fasted human small intestine, such as the migrating motor complex, and aids in the identification of the postprandial motor pattern. Motor patterns are defined in terms of properties such as contraction frequency and propagation. In a validation procedure using conventional manual analysis, the program correctly identifies the number of individual contractions with a 98% confidence interval and also correctly recognises 96% of phase 3 motor activity.

Although human postinflammatory dysmotility is known, so far animal studies have primarily investigated changes during inflammation. Here, we focused on postinflammatory changes in rat jejunal myenteric plexus and jejunal motility. Evolution of ethanol/2,4,6-tri-nitrobenzene sulphonic acid (TNBS)-induced inflammation was assessed histologically and by measuring myeloperoxidase activity (MPO). Electromyography and immunohistochemistry were performed 1 week after ethanol/TNBS and also after N(G)-nitro-L-arginine methyl ester (L-NAME) administration. Ethanol/TNBS induced a transient inflammation, with normalization of MPO and histological signs of an early phase of recovery after 1 week. The number of cholinergic neurones was not altered, but myenteric neuronal nitric oxide synthase (nNOS)-immunoreactivity was significantly lower in the early phase of recovery after TNBS compared with water (1.8 +/- 0.2 vs 3.5 +/- 0.2 neurones ganglion(-1), P < 0.001). Interdigestive motility was disrupted with a loss of phase 1 quiescence, an increase of migrating myoelectric complex cycle length, a higher number of non-propagated activity fronts and a decrease of adequately propagated phase 3 s after TNBS. Administration of L-NAME resulted in a similar disruption of interdigestive motility patterns. In the early phase of recovery after ethanol/TNBS-induced jejunal inflammation, a loss of motor inhibition occurs due to a decrease of myenteric nNOS activity. These observations may provide a model for early postinflammatory dysmotility syndromes.