Intestinal motility during acute Yersinia enterocolitica enteritis in rabbits

To determine if Yersinia enterocolitica (YE) enteritis is associated with an alteration of intestinal myoelectric and motor activity, and with an increased rate of aboral transit, New Zealand white rabbits (500-900 g) were surgically prepared with ileal bipolar electrodes and a manometry catheter adjacent to the distal electrode. One week later animals were inoculated with 10(10) organisms of YE in 10 mL NaHCO3 (infected group) or 10 mL NaHCO3 (sham-infected pair-fed and control groups). Daily food intake, weight gain, YE excretion, and stool pattern were noted. Intestinal myoelectric and motor activity over a 6- to 8-h period before and 3, 6, and 14 days after inoculation was compared in infected (I), pair-fed (PF), and control (C) groups. Intestinal transit was evaluated in I and C animals on days 3 and 6 after inoculation by measuring the distribution in the intestinal lumen of 51Cr 20 min after it was instilled directly into the jejunum. Infected animals exhibited diarrhea, fecal excretion of YE, and significantly decreased food intake, weight gain, and survival (11.4 +/- 0.6 days). Infection was associated with a significant (p less than 0.05) decrease in both the cycle period of the migrating myoelectric complex (MMC) and the total number of single, paired, and (or) clustered contractions per MMC, and a significant (p less than 0.001) increase in duration of phase III of the MMC. There was no change in intestinal slow wave frequency (19 cycles/min), motility index per MMC, or the percentage of contractions that propagated in an orad (7%) or aboral (69%) direction or that appeared stationary (25%).(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of splanchnectomy on jejunal motility and fos expression in brain stem after intestinal anaphylaxis in rat

This study was to determine whether alterations in jejunal motility observed after antigen challenge of sensitized rats occurred after extirpation of the celiac-superior mesenteric ganglia. Hooded-Lister rats were prepared with an intact or extirpated celiac-superior mesenteric ganglion, an isolated Thiry-Vella loop of ileum for instillation of antigen, and jejunal electrodes for myoelectric recording. Animals were sensitized by injection of 10 microg egg albumin (EA, ip), and specific anti-EA IgE titers were determined to be >1:64. In both control and splanchnectomized rats, normal fasting migrating myoelectric complexes (MMC) were observed before challenge with EA. MMCs were disrupted, and diarrhea was observed immediately after EA challenge of control but not splanchnectomized animals. Brain stems were removed and processed for Fos immunoreactivity. The absence of perivascular neuropeptide Y immunoreactivity in the submucosa was used to confirm the success of splanchnectomy. The number of Fos-immunoreactive neuronal nuclei was significantly reduced in the brain stem after splanchnectomy. Thus the mesenteric sympathetic ganglia are an integral part of the extramural neuronal pathways required for altered motility in this model of intestinal anaphylaxis.     

Ghrelin stimulates motility in the small intestine of rats through intrinsic cholinergic neurons

BACKGROUND AND PURPOSE: Ghrelin is a peptide discovered in endocrine cells of the stomach. Since ghrelin mRNA expression and plasma levels are elevated in the fasting state, we investigated the effects of ghrelin on the interdigestive migrating myoelectric complex (MMC) in the small intestine in vivo and compared with motor effects of ghrelin in vitro. Methods: Sprague-Dawley rats were supplied with a venous catheter and bipolar electrodes in the duodenum and jejunum for electromyography of small intestine in awake rats. In organ baths, isometric contractions of segments of rat jejunum were studied. RESULTS: Ghrelin dose-dependently shortened the MMC cycle length at all three recording points. At the duodenal site, the interval shortened from 17.2+/-2.0 to 9.9+/-0.8 min during infusion of ghrelin (1000 pmol kg(-1) min(-1)) and at the jejunal site from 17.5+/-2.2 to 10.5+/-0.8 min. Ghrelin contracted the muscle strips with a pD2 of 7.97+/-0.47. Atropine (10(-6) M) in vitro and (1 mg kg(-1)) in vivo blocked the effect of ghrelin. CONCLUSION: Ghrelin stimulates interdigestive motility through cholinergic neurons. Ghrelin also stimulates motility, in vitro, suggesting that ghrelin receptors are present in the intestinal neuromuscular tissue and mediate its effects via cholinergic mechanisms.     

Variations of plasma immunoreactive motilin, pancreatic polypeptide, gastrin and somatostatin along the duodenal motility cycle in the pig

The peripheral plasma concentrations of immunoreactive motilin, pancreatic polypeptide (PP), somatostatin and gastrin were measured in 7 pigs fasted to 24 h and subsequently fed a standard meal. Plasma motilin peaked during the last part of phase II activity of the migrating myoelectric complex (MMC) sequence (25.2 +/- 2.3 pM), the lowest value being recorded during phase I (10.6 +/- 1.5 pM) after a 24 h fast. Plasma motilin remained at a low level during the digestive pattern of duodenal activity, no fluctuation occurring when the first postprandial MMC recurred. At variance analysis, gastrin and PP were not released phasically with MMC in the fasting state, while at autocovariance both peptides tended to fluctuate during the MMC sequence with positive and negative peaks at regular intervals along MMC cycles. No variation of plasma somatostatin was observed in the fasting animals. These findings argue against a major role of circulating PP, gastrin and somatostatin-like components in the control of fasted and post absorptive duodenal motility in pigs while the role of motilin remains equivocal.     

The effect of food protein-induced intestinal anaphylaxis on rate of transit

The aim of this study was to determine if the altered jejunal motility previously demonstrated in this animal model of food protein-induced intestinal anaphylaxis is (a) a localized (the jejunal site of challenge), or a generalized response of the small intestine, and (b) associated with more rapid aboral transit of intraluminal contents. Hooded-Lister rats, 100-150 g in weight, were sensitized by intraperitoneal injection of 10 micrograms egg albumin. Control rats were sham-sensitized. On day 7 rats were surgically prepared with six bipolar electrodes from duodenum to ileum and (or) a jejunostomy tube was positioned at the ligament of Treitz. On day 14, after an 18-h fast, recording of myoelectric activity were obtained from four sensitized animals with electrodes from duodenum to ileum during a control period for 45 min after saline challenge and for 45 min after antigen challenge. Control (n = 25) and sensitized (n = 31) animals with only a jejunostomy had Na2 51CrO4 instilled through the jejunostomy in 0.5 mL of saline, with or without egg albumin, either during a fast or after a standard meal. Propulsion of isotope through the small bowel was allowed to progress for 15 min, the animals were sacrificed, and their gut was removed for division into eight equal segments of small intestine, cecum, and remaining colon. The radioactivity of each segment was determined in a gamma counter.(ABSTRACT TRUNCATED AT 250 WORDS)     

Travel stress alters the intestinal migrating myoelectric complex in rats: antagonist effect of trimebutine.

A novel stress model was developed that may closely resemble a real-life situation. Intestinal motility was monitored in rats before and after a 12 hour train voyage (travel stress). Travel stress reduced the duration of phase III of the intestinal MMC by 30% (3.2 +/- 0.3 vs 4.7 +/- 0.6 min; p less than 0.001) while the durations of phase I and II were unaffected. This effect persisted for two days. Phase III duration returned to basal values after 3 days indicating a reversible alteration on intestinal migrating myoelectric complex (MMC). The infusion of trimebutine at a flow rate of 166 micrograms/kg/h during the stress exposure abolished the changes observed in the duration of phase III of the MMC; the infusion of diazepam (16.6 micrograms/kg/h) had no effect. These results indicate that the travel stress model may be similar to common life events that induce alterations of intestinal motility. Furthermore, trimebutine prevented the reduction of phase III duration induced by travel stress suggesting its possible action on mechanisms involved in the mediation of the stress-induced intestinal motility changes.     

Intestinal motility responses to insulin and glucagon in streptozotocin diabetic rats

Myoelectrical and mechanical activities were chronically recorded by use of nichrome electrodes and miniaturized strain-gage transducers sutured on the serosa of the antrum, the duodenum, and the jejunum. In a first experiment (n = 6 rats) the early (0-6 h) and late (greater than 4 days) effects of streptozotocin (65 mg/kg i.v.) was recorded. In addition, the effect of insulin (1-5 IU/kg) and glucagon (6-200 micrograms/kg) administered intravenously were studied separately each in groups of seven normal and streptozotocin-induced diabetic-fed and fasted rats. The results indicated that within the 30 min following streptozotocin administration there was a significant stimulation of the duodenal and jejunal motility lasting 46 +/- 8 min. When diabetes was established as shown by the basal blood glucose level obtained in those rats (2.30 +/- 0.84 g/L), a progressive decrease of the frequency of the migrating myoelectric complex was observed along with a disorganization of the regular spiking activity phases without disturbing the basal electrical rhythm. Comparing with the basal level, a significant increase in the gastrointestinal motility indexes (MI) appeared both in fasted (p less than 0.01) and fed (p less than 0.05) normal animals, 13.1 +/- 1.6 min after an i.v. injection of 1 IU/kg insulin. Motor effects of glucagon were related to the dose. When used at 25 microgram/kg a disorganization of the spiking activity was observed with a stimulation of the contractile activity in the jejunum. At higher dosages, i.e., 100 micrograms/kg, it induced an immediate and significant decrease of motility at any level tested and lasting up to 20 +/- 7 min. The motility responses to both hormones were lower in diabetic than in normal rats.     

The effect of intestinal anaphylaxis on postprandial motility in the rat

We have previously utilized a rat animal model to demonstrate that challenge of fasted sensitized animals with antigenic food protein is associated with diarrhea and altered intestinal myoelectric and motor activities. In this paper we examine the effect of intestinal anaphylaxis on postprandial motility in the same animal model. Hooded Lister rats were sensitized (S) by intraperitoneal injection of 10 micrograms egg albumin (i.e., antigen (Ag) and compared with sham-sensitized controls (C). Seven days later, three bipolar jejunal electrodes and a jejunostomy tube, for motility recording and Ag administration, were implanted. On day 14, intestinal myoelectric and motor activities were measured in fed animals before and after intraluminal challenge with Ag (100 mg egg albumin/0.5 mL saline) or placebo (P; 0.5 mL saline). Specific immunoglobulin E serum titres were greater than or equal to 1:64 in S animals, while C animals showed no response. None of the C animals challenged with P or Ag and none of the S animals challenged with P defecated after challenge, but all the S animals challenged with Ag developed diarrhea (p less than 0.001). There was no disruption or alteration of the fed motility pattern in C animals challenged with P or Ag, or S animals challenged with P. In fed S animals challenged with Ag the fed motility pattern persisted, but there was a significant (p less than 0.05) increase in the number of high-amplitude aborally propagating clustered contractions, where the phasic contractile activity was superimposed on a sustained tonic elevation of intraluminal pressure lasting 5-10 s.(ABSTRACT TRUNCATED AT 250 WORDS)     

5-羟色胺和胃动素在狗小肠移行性复合运动调控中的作用

应用慢性植入小肠腔外应力传感器记录清醒狗小肠移行性复合运动（ＭＭＣ）。在颈外静脉和支配１０￣１５ｃｍ肠段的空肠动脉内分别放置－硅胶管以备灌流药物的取血样品用。本研究观察了静脉和动脉注射药物对小肠ＭＭＣ的影响及ＭＭＣ不同时相血浆５－羟色胺（５－ＨＴ）和胃动素的浓度变化。结果表明：（１）ＭＭＣ不同时相血浆５－ＨＴ和胃动素浓度呈周期性变化,５－ＨＴ峰值在胃动素峰值之前出现。血浆５－ＨＴ浓度在ＭＭＣⅡ相后     

Influence of microbial species on small intestinal myoelectric activity and transit in germ-free rats

The effect of an intestinal microflora consisting of selected microbial species on myoelectric activity of small intestine was studied using germ-free rat models, with recording before and after specific intestinal colonization, in the unanesthetized state. Intestinal transit, neuropeptides in blood (RIA), and neuromessengers in the intestinal wall were determined. Clostridium tabificum vp 04 promoted regular spike burst activity, shown by a reduction of the migrating myoelectric complex (MMC) period from 30.5 +/- 3.9 min in the germ-free state to 21.2 +/- 0.14 min (P < 0.01). Lactobacillus acidophilus A10 and Bifidobacterium bifidum B11 reduced the MMC period from 27.9 +/- 4.5 to 21.5 +/- 2.1 min (P < 0.02) and accelerated small intestinal transit (P < 0.05). Micrococcus luteus showed an inhibitory effect, with an MMC period of 35.9 +/- 9.3 min compared with 27.7 +/- 6.3 min in germ-free rats (P < 0.01). Inhibition was indicated also for Escherichia coli X7 gnotobiotic rats. No consistent changes in slow wave frequency were observed. The concentration of neuropeptide Y in blood decreased after introduction of conventional intestinal microflora, suggesting reduced inhibitory control. Intestinal bacteria promote or suppress the initiation and aboral migration of the MMC depending on the species involved. Bacteria with primitive fermenting metabolism (anaerobes) emerge as important promoters of regular spike burst activity in small intestine.     

Motilin and the vagus in dogs

The aim of this work was to determine the influence of the vagus on the circulating levels of immunoreactive (IR) motilin. Five mongrel dogs were equipped with chronically implanted electrodes in the small intestine to record the myoelectrical activity. The release of IR motilin during fasting, after a meal, and during an infusion of insulin was studied before and after truncal vagotomy at the diaphragmatic level. When tested at least two weeks after the operation, the motility pattern of the small intestine and the secretion of IR motilin remained unaltered by vagal section. Cyclic increases in IR motilin associated with phase III's of the interdigestive myoelectric complexes were still observed after vagotomy (maximum levels of IR motilin: 250 +/- 37 versus 239 +/- 19 fmol X mL-1, not significant), and they were still abolished by feeding or by insulin. However, an inhibitory influence can probably be mediated by the vagus since, in normal animals, vagal stimulation by a "modified sham feeding" (tease feeding or presentation of food) at the beginning of a period of phase III activity promptly interrupted this part of the complex and decreased significantly the release of IR motilin by about 20%. The release of motilin is not chronically altered by distal vagotomy in dogs.     

Central effects of growth hormone-releasing factor (GRF) on intestinal motility in dogs: involvement of dopaminergic receptors

The effects of intracerebroventricular (ICV) and intravenous (IV) administration of human pancreatic growth hormone-releasing factor (hpGRF) on gastro-intestinal motility were examined in fasted and fed conscious dogs equipped with chronically implanted strain-gauges on the antrum and the jejunum. During the fasted state, hpGRF injected ICV at 0.1 micrograms . kg-1 or IV at 0.5 micrograms . kg-1 did not affect the cyclic occurrence of the migrating motor complex (MMC). This pattern was normally disrupted for 8-10 hours by a daily standard meal. Injected ventricularly (0.1 micrograms . kg-1) but not intravenously (0.5 micrograms . kg-1) 10-15 min after the daily meal, hpGRF significantly reduced (p less than 0.01) the duration of the jejunal fed pattern (2.0 +/- 1.4 vs. 8.4 +/- 1.1 hours for control) but not that of the stomach. This effect persisted when hpGRF (0.1 micrograms . kg-1 ICV) was administered after indomethacin (2 mg . kg-1 IM), naltrexone (0.1 mg . kg-1 IV) or domperidone (1 mg . kg-1 IV) but was abolished by a previous IV injection of metoclopramide (1 mg . kg-1). It was concluded that hpGRF is able to act centrally to control the pattern of jejunal motility in fed but not in fasted dog, its effect being probably mediated through dopaminergic pathways.     

5-Hydroxytryptamine affects rat migrating myoelectric complexes through different receptor subtypes: evidence from 5-hydroxytryptophan administration

The effect of the serotonin precursor 5-hydroxytryptophan (5-HTP) on jejunal migrating myoelectric complexes (MMCs) was investigated in conscious rats. Subcutaneous administration of low doses of 5-HTP (1-2 mg/kg) shortened the period between migrating complexes, whereas high doses of the compound (4-8 mg/kg) disrupted the MMC pattern. The serotonin (5-HT2) antagonist methysergide (8 mg/kg s.c.) did not alter basal MMC, neither did it prevent the effect of a low dose of 5-HTP; conversely, it antagonized the disruption due to the high dose. The 5-HT3 antagonist ICS 205-930 (30 micrograms/kg s.c.) decreased MMC frequency; administration of 2 mg/kg 5-HTP following ICS 205-930 brought the frequency of myoelectric complexes back to basal values. Both effects of 5-HTP were prevented by the decarboxylase inhibitor benserazide (85 mg/kg i.p.), which per se caused a transient inhibition of spiking activity. The results suggest that rat MMCs can be influenced in a composite fashion by progressively increasing concentrations of 5-HT, which in turn activate different receptor subtypes. A peripheral neuronal receptor, probably belonging to the 5-HT3 subclass, mediates the increase in MMC frequency observed after low doses of 5-HTP; higher levels of serotonin activate 5-HT2 receptors, causing disruption of cycling activity. Additionally, 5-HT3 receptors, but not 5-HT2, appear to be relevant for the regulation of the MMC pattern by the endogenous amine.     

Circadian coupling between pancreatic secretion and intestinal motility in humans

Human interdigestive intestinal motility follows a circadian rhythm with reduced nocturnal activity, but circadian pancreatic exocrine secretion is unknown. To determine whether circadian changes in interdigestive pancreatic secretion occur and are associated with motor events, pancreatic enzyme outputs, proximal jejunal motility, and plasma pancreatic polypeptide concentrations were measured during consecutive daytime and nighttime periods (12 h each) in seven healthy volunteers using orojejunal multilumen intubation. Studies were randomly started in the morning or evening. Nocturnally, motility decreased (motor quiescence: 67 +/- 22 vs. 146 +/- 37 min; motility index: 3.59 +/- 0.33 vs. 2.78 +/- 0.40 mmHg/min; both P < 0.05) but amylase output increased (273 +/- 78 vs. 384 +/- 100 U/min; P < 0.05) and protease output remained unchanged (P > 0.05); consequently, enzyme/motility ratio increased. Amylase outputs were always lowest during phase I. Motor but not pancreatic circadian activities were associated with sleep. Pancreatic polypeptide plasma concentrations were unchanged. Consequently, intestinal motor and pancreatic exocrine functions may have different circadian rhythms, i.e., decreased motor and stable secretory activity during the night. However, the association between individual phases of interdigestive motor and secretory activity is preserved. The nocturnal increase in enzyme/motility ratio is probably not caused by increased cholinergic tone.     

Central origin on the excito-motric action of morphine on intestine]

In ewew fitted with a cerebro-ventricular cannula and equipped with extra-cellular bipolar electrodes on the antrum and proximal small intestine, an intraventricular injection of morphine at a dose (40 micrograms/kg) ineffective peripherally was followed within 1 min by an increased spike activity of the duodenum without disruption of the occurrence of migrating myoelectric complexes. This effect was paralleled by a reduction of antral motility and abolished by small intraventricular doses of nalorphine. After an intravenous injection of large doses of the drug drug (0.8 mg/kg), spike activity was increased at both jejunal and duodenal level without changes in the antrum and followed by a long-lasting disorganization of the motor profile. The results suggested a centrally mediated gastro-duodenal effect of morphine.     

Antroduodenal motility in chronic pancreatitis: are abnormalities related to exocrine insufficiency?

In patients with chronic pancreatitis (CP) the relation among exocrine pancreatic secretion, gastrointestinal hormone release, and motility is disturbed. We studied digestive and interdigestive antroduodenal motility and postprandial gut hormone release in 26 patients with CP. Fifteen of these patients had pancreatic insufficiency (PI) established by urinary para-aminobenzoic acid test and fecal fat excretion. Antroduodenal motility was recorded after ingestion of a mixed liquid meal. The effect of pancreatic enzyme supplementation was studied in 8 of the 15 CP patients with PI. The duration of the postprandial antroduodenal motor pattern was significantly (P < 0.01) prolonged in CP patients (324 +/- 20 min) compared with controls (215 +/- 19 min). Antral motility indexes in the first hour after meal ingestion were significantly reduced in CP patients. The interdigestive migrating motor complex cycle length was significantly (P < 0.01) shorter in CP patients (90 +/- 8 min) compared with controls (129 +/- 8 min). These abnormalities were more pronounced in CP patients with exocrine PI. After supplementation of pancreatic enzymes, these alterations in motility reverted toward normal. Digestive and interdigestive antroduodenal motility are abnormal in patients with CP but significantly different from controls only in those with exocrine PI. These abnormalities in antroduodenal motility in CP are related to maldigestion.     

Localization and effects of orexin on fasting motility in the rat duodenum

The orexins [orexin A (OXA) and orexin B (OXB)] are novel neuropeptides that increase food intake in rodents. The aim of this study was to determine the distribution of orexin and orexin receptors (OX1R and OX2R) in the rat duodenum and examine the effects of intravenous orexin on fasting gut motility. OXA-like immunoreactivity was found in varicose nerve fibers in myenteric and submucosal ganglia, the circular muscle, the mucosa, submucosal and myenteric neurons, and numerous endocrine cells of the mucosa. OXA neurons displayed choline acetyltransferase immunoreactivity, and a subset contained vasoactive intestinal peptide. OXA-containing endocrine cells were identified as enterochromaffin (EC) cells based on the presence of 5-hydroxytryptamine immunoreactivity. OX1R was expressed by neural elements of the gut, and EC cells expressed OX2R. OXA at 100 and 500 pmol x kg(-1) x min(-1) significantly increased the myoelectric motor complex (MMC) cycle length compared with saline. Similarly, OXB increased the MMC cycle length at 100 pmol x kg(-1) x min(-1), but there was no further effect at 500 pmol x kg(-1) x min(-1). We postulate that orexins may affect the MMC through actions on enteric neurotransmission after being released from EC cells and/or enteric neurons.     

绒毛膜促性腺激素及孕酮对大鼠小肠移行性综合肌电的影响

于去卵巢大鼠小肠的不同部位植入铂金丝单极电极,观察了绒毛膜促性腺激素(HCG)及孕酮对其移行性综合肌电(MMC)的影响。结果为:(1) 静注HCG后,十二指肠及空肠上段出现典型的与妊娠有关的MMC改变,即MMC的周期被间断出现且不规则延长的Ⅱ相所打乱。(2) 肌注孕酮后,十二指肠MMC的Ⅰ相和Ⅱ相时程均显著延长,但MMC的周期性无明显紊乱。(3) 在肌注孕酮的基础上加注HCG后,MMC的变化在特征上与单独注射HCG时相同,在范围上扩大到整个小肠。上述结果提示,在大鼠,HCG可引起典型的与妊娠有关的MMC活动紊乱;当有孕酮存在时,HCG的这一效应进一步增强。     

Glucagon-like peptide-1 analogue LY315902: effect on intestinal motility and release of insulin and somatostatin

LY315902 is an analogue of GLP-1 that yields a reduced clearance and longer half-life. The aim of the study is to assess the effect of LY315902 on fasting gastrointestinal motility, somatostatin and insulin release. Sprague-Dawley rats were fitted with three bipolar electrodes, 15, 25 and 35 cm distal to the pylorus. The effect of LY315902 and GLP-1 on migrating myoelectric complex (MMC) cycle length, duration and propagating velocity of activity fronts was studied for 60 min in conscious animals. The effect of LY315902 and GLP-1 on fasting small bowel motility was dose-dependent and treatment with exendin (9-39)amide, a GLP-1 receptor antagonist, together with LY315902 and GLP-1 completely antagonised the inhibitory effect of LY315902 and GLP-1 on fasting small bowel motility. Pretreatment with the nitric oxide (NO) synthase inhibitor N(omega)-nitro-L-arginine (L-NNA) partly blocked the action of both LY315902 and GLP-1. Plasma insulin concentrations were not different from controls during infusion of LY315902 or GLP-1, while somatostatin concentrations were significantly higher during LY315902 and GLP-1 compared to saline. LY315902 has a longer duration of inhibitory action on the MMC than GLP-1, albeit similar effects on plasma insulin and somatostatin concentrations. The effect of LY315902 on motor control is mediated through the GLP-1 receptor and seems partly dependent on the L-arginine/NO pathway.     

Tachykinin-stimulated small bowel myoelectric pattern: sensitization by NO inhibition, reversal by neurokinin receptor blockade

Tachykinins stimulate motility whereas NO inhibits motility in the gastrointestinal tract. AIM: To investigate if inhibition of NO production sensitizes myoelectric activity to subthreshold doses of tachykinins in the small intestine of awake rats. METHODS: Rats were supplied with a venous catheter and bipolar electrodes at 5, 15 and 25 cm distal to pylorus for electromyography of small intestine. The motor responses were evaluated using pattern recognition. Substance P and neurokinin A dose-dependently stimulated gut motility, with neurokinin A being more potent than substance P. Therefore, neurokinin A was chosen and administered under baseline conditions and 45-60 min after N(omega)-nitro-L-arginine (L-NNA) 1 mg kg(-1), with or without pretreatment with L-arginine 300 mg kg(-1). In addition, myoelectric activity effects of neurokinin A in conjunction with L-NNA were studied before and after administration of the tachykinin receptor antagonists, SR140333 (NK1), SR48968 (NK2) and SR142801 (NK3), each at 2.5 mg kg(-1). RESULTS: Dose-finding studies verified 10 pmol kg(-1) min(-1) to be the threshold dose at which NKA caused phase II-like activity in a low percentage of experiments (12%, n=41). This dose was therefore used in combination with L-NNA for sensitization experiments of gut myoelectric activity. In experiments where NKA-induced no response, pretreatment with L-NNA led to phase II-like activity in 9 of 18 (50%, p<0.05) experiments. Co-administration of SR140333 and SR48968 abolished this effect. CONCLUSION: NO counteracts the stimulatory effect of tachykinins on small bowel myoelectric activity in the rat. Inhibition of the L-arginine/NO pathway sensitizes the gut to tachykinin-stimulated motor activity.