Biomedical subjects

J Janssens

Publications and source records attributed to J Janssens.

At least 55 records · Page 3Linked to original sources

PubMed2002

Electrical behaviour of interleukin-1 beta (IL-1 beta) and prostaglandin-E2 (PGE2) on colonic myenteric neurones.

Abstract Intracellular recordings were used to examine the effects on electrical and synaptic behaviour of interleukin (IL)-1beta and prostaglandin E2(PGE2) on myenteric neurones of the guinea-pig colon. Application of IL-1beta and PGE2resulted in a concentration-dependent slow depolarization with enhanced spike discharge in, respectively, 45% (21/47) and 83% (33/41) of the impaled colonic neurones. Administration of IL-1beta in three neurones (6%) elicited a hyperpolarization. Responses remained during tetrodotoxin application, indicative of a direct effect of both substances on the impaled neurones. The effects of IL-1beta remained in the presence of indomethacine, a prostaglandin synthase inhibitor. Responses were seen in both nitric oxide synthase- and choline acetyl transferase-immunoreactive neurones. IL-1beta evoked a 26% reduction of the fast excitatory postsynaptic potential. These results indicate that the application of IL-1beta and PGE2evoke direct excitatory actions on a subset of myenteric neurones. For IL-1beta, direct inhibition and presynaptic inhibition of the fast excitatory postsynaptic potential has also been found. In the distal colon, responses to IL-1beta are not mediated through PGE2pathways.

Animals↗

PubMed2002

Role of nitric oxide in the gastric accommodation reflex and in meal induced satiety in humans.

AIMS: In humans, impaired gastric accommodation is associated with early satiety and weight loss. In animals, accommodation involves activation of gastric nitrergic neurones. Our aim was to study involvement of nitric oxide in gastric accommodation and in meal induced satiety in humans. METHODS: The effect of N(G)-monomethyl-L-arginine (L-NMMA) 4 mg/kg/h and 8 mg/kg/h on gastric compliance, on sensitivity to distension, and on gastric accommodation was studied with a barostat in double blind, randomised, placebo controlled studies. The effect of L-NMMA 8 mg/kg/h on meal induced satiety was studied using a drinking test. RESULTS: L-NMMA had no significant effect on fasting compliance and sensitivity. Ingestion of a meal induced a relaxation of 274 (15) ml which was significantly smaller after L-NMMA 4 mg/kg/h (132 (45) ml; p=0.03) or L-NMMA 8 mg/kg/h (82 (72) ml; p=0.03). L-NMMA 8 mg/kg/h significantly decreased the amount of food ingested at maximum satiety from 1058 (67) to 892 (73) kcal (p<0.01). CONCLUSION: In humans, fasting gastric tone and sensitivity to distension are not influenced by nitric oxide synthase inhibition, but the gastric accommodation reflex involves activation of nitrergic neurones. Inhibition of nitric oxide synthase impairs accommodation and enhances meal induced satiety.

Adaptation, Physiological↗

PubMed2001

Effect of intranasal sumatriptan on gastric tone and sensitivity to distension.

Sumatriptan is able to improve symptoms of early satiety in dyspeptic patients by relaxing the gastric fundus. The aim of this study was to verify the efficacy of intranasal administration of sumatriptan on gastric sensory motor function, in order to provide a new pharmacotherapeutic approach to functional dyspepsia. Thirteen healthy subjects were investigated twice on separate days. A gastric barostat was used to study the effect of placebo and sumatriptan, 20 mg intranasally, on basal fundic tone. In addition, stepwise isobaric distensions were performed and perception was measured before and after administration of drugs. Placebo had no effect on gastric tone and on perception. Sumatriptan caused a small, but short-lasting gastric relaxation and had no significant effect on sensitivity to distension and gastric compliance. Unlike the subcutaneous formulation, the intranasal administration of sumatriptan had no effect on gastric sensory motor functions, and this probably reflects a low biovailability of intranasally administered sumatriptan.

Administration, Intranasal↗

PubMed2001

Contractile effects and intracellular Ca2+ signalling induced by motilin and erythromycin in the circular smooth muscle of human colon.

Motilin has excitatory effects on the colon of the rabbit and the dog, but little is known of its effect on the human colon. The aim of this study was to investigate the effects induced by motilin and erythromycin A (EMA) on muscle strips and on single cells from primary cultures from human colon. Isotonic contraction was recorded in circular muscle strips from macroscopically normal resection specimens of patients operated on for colonic neoplasm. Agonist-induced intracellular Ca2+ ([Ca2+]i) signalling was studied in primary cultures of colonic smooth-muscle cells using the ratiometric Ca2+ indicator Indo 1, on a laser-scanning confocal epifluorescence microscope. In circular muscle strips, norleucine13-porcine motilin ([Nle13]-pm)and EMA induced tonic contractions with an EC50 of 92 +/- 21 nmol L(-1) and 31 +/- 16 micromol L(-1), respectively. The maximal contraction was 21 +/- 4% (motilin) and 33 +/- 12% (EMA) of the response to 10(-4) mol L(-1) acetylcholine (ACh). The motilin antagonist OHM-11526 (10(-5.5) mol L(-1)) abolished the effects of both [Nle13]-pm and EMA. Neither tetrodotoxin (10(-5.5) mol L(-1)), L-nitro-D-arginine methyl ester (L-NAME) (10(-3.5) mol L(-1)) nor guanethidine (10(-5) mol L(-1)) interfered with the effects of [Nle13]-pm or EMA. [Nle13]-pm (10(-11)-10(-6) mol L(-1)) induced rises of [Ca2+]i in cultured colonic myocytes. At 10(-6) mol L-1, 94% of the cells responded, and half of the cells responded at 1.4 nmol L(-1) [Nle13]-pm. 81% (35/43) and 95% (75/79) responded to EMA (10(-6) mol L(-1)) and acetylcholine (ACh, 10(-4) mol L(-1)), respectively. The motilin antagonist GM-109 inhibited motilin- and EMA-induced [Ca2+]i rises. In the absence of extracellular Ca2+, only 13% (7/52) of the cells responded to [Nle13]-pm (10(-6) mol L(-1)) vs. 90% (47/52) to ACh (10(-4) mol L(-1)). Motilin and EMA have direct excitatory effects on circular smooth muscle from the human colon and these effects are mediated via a smooth-muscle motilin receptor. These findings suggest that motilin may regulate colonic motility and that motilides may have therapeutic potential for the treatment of colonic hypomotility.

Acetylcholine↗

PubMed2001

Effect of sildenafil, a phosphodiesterase-5 inhibitor, on oesophageal peristalsis and lower oesophageal sphincter function in cats.

The propagation of oesophageal peristaltic contractions and lower oesophageal sphincter (LOS) relaxation depends on neural release of nitric oxide (NO) which acts to increase intracellular cGMP. Sildenafil, a phosphodiesterase-5 inhibitor that increases cGMP, reduces basal LOS pressure in patients with achalasia. We investigated the effect of sildenafil on the propagation of oesophageal contractions and LOS relaxation in the cat. Oesophageal manometry was performed in five cats under light sedation. Peristaltic contractions were monitored at 1, 2, 3, 4 and 8 cm proximal to the LOS, at the LOS using a Dent sleeve, and at 3 cm distal to the upper oesophageal sphincter. Swallow-induced oesophageal contractions and LOS relaxation were recorded during 30 min before and 30 min after intravenous administration of sildenafil. Sildenafil reduced the amplitude of oesophageal contractions only in the smooth muscle oesophagus. The latency from swallow to distal oesophageal contractions was significantly delayed. LOS pressure was significantly reduced but the relaxation nadir was not modified by sildenafil. Sildenafil has profound effects on oesophageal motility: it modifies propagation and amplitude of oesophageal contractions and reduces LOS pressure. Slowing down the propagation of contractions in the transitional zone between the striated and smooth muscle can be a useful tool in patients with segmental aperistalsis or intermittent simultaneous contractions, while the effect on the LOS can benefit patients with achalasia.

Animals↗

PubMed2001

Free cytosolic Ca2+ recordings from myenteric neurones in multilayer intestinal preparations.

The ability to simultaneously monitor different myenteric neurones in a multilayer preparation may enhance our understanding of the enteric nervous system. Longitudinal muscle myenteric plexus preparations were mounted in recording chambers with a coverslip base and loaded with Indo-1-AM. cytosolic Ca2+ concentration ([Ca2+]i); changes were recorded at room temperature with a confocal microscope. In addition to mechanical (pressure-ring) and pharmacological (nifedipine) reduction of muscle contractions, purpose-designed software was developed to reposition regions of interest and avoid artefacts. Confocal scanning permitted optical selection of single cell layers. High K+ depolarization, used to distinguish between excitable and nonexcitable cells, caused a synchronous [Ca2+]i rise in 84.3% of the ganglion cells. Acetylcholine, substance P and serotonin (all at 10(-5) mol L(-1)) induced transient [Ca2+]i changes in subpopulations of myenteric neurones (45.1%, 42.9 and 21.9%, respectively). In addition to immediate responses to agonists, delayed [Ca2+]i changes were also recorded, suggesting the presence of both directly activated and synaptically driven neurones. Functionally identified neurones and other cells in close apposition to the ganglia (interstitial cells of Cajal) could also be studied. This study demonstrates the potential of optical Ca2+ recordings to monitor spread of activity in myenteric neurones and to study their interaction with non-neuronal targets.

Acetylcholine↗

PubMed2001

Acid, nonacid, and gas reflux in patients with gastroesophageal reflux disease during ambulatory 24-hour pH-impedance recordings.

BACKGROUND & AIMS: Gastroesophageal reflux can be acid, nonacid, pure liquid, or a mixture of gas and liquid. We investigated the prevalence of acid and nonacid reflux and the air-liquid composition of the refluxate in ambulant healthy subjects and patients with reflux disease (GERD). METHODS: Twenty-four-hour ambulatory recordings were performed in 30 patients with symptomatic GERD and erosive esophagitis and in 28 controls. Esophageal pH and impedance were used to identify acid reflux (pH drop below 4.0), minor acid reflux (pH drop above 4.0), nonacid reflux (pH drop less than 1 unit + liquid reflux in impedance), and gas reflux. RESULTS: The total rate of gastroesophageal reflux episodes was similar in patients and controls. Patients with GERD had a higher proportion (45% vs. 33%) and rate of acid reflux than controls (21.5 [9-35]/24 h vs. 13 [6.5-21]/24 h; P < 0.05). One third of reflux events was nonacid in both groups. Mixed reflux of gas and liquid was the most frequent pattern with gas preceding liquid in 50%-80% of cases. Pure liquid reflux was more often acid in patients with GERD than controls (45% vs. 32%; P < 0.05). CONCLUSIONS: Reflux of gastric contents was similarly frequent in patients with GERD and controls. Although there was no difference in the overall number of reflux episodes, more acidic reflux occurred in symptomatic patients with GERD, suggesting differences in gastric acid secretion or distribution.

Adult↗

PubMed2001

Symptoms associated with hypersensitivity to gastric distention in functional dyspepsia.

BACKGROUND & AIMS: Hypersensitivity to gastric distention has been reported in functional dyspepsia, but its characteristics and relevance to symptoms remain unclear. The aim of this study was to define hypersensitivity to gastric distention and its association to specific symptoms in functional dyspepsia. METHODS: We used a gastric barostat to study sensitivity to gastric distention in 80 healthy subjects and in 160 functional dyspepsia patients. Demographic characteristics, gastric emptying, Helicobacter pylori status, gastric accommodation, and a dyspepsia symptom score were obtained from all patients and the relationship with visceral sensitivity was assessed using univariate and multivariate analysis. RESULTS: The increase of intra-balloon pressure over intra-abdominal pressure needed to induce discomfort or pain is the most appropriate expression of sensitivity to gastric distention because it yields a meaningful lower range of normal and it is independent from age and body mass index. Hypersensitivity to gastric distention was found in 34% of the patients, who did not differ from the other patients in demographic and other pathophysiological characteristics. Hypersensitivity to distention was associated with a higher prevalence of postprandial pain, belching, and weight loss. CONCLUSIONS: Hypersensitivity to gastric distention is present in a subset of functional dyspepsia patients. It is associated with symptoms of postprandial epigastric pain, belching, and weight loss.

Abdominal Pain↗

PubMed2001

Reproducibility of gastric barostat studies in healthy controls and in dyspeptic patients.

OBJECTIVES: Gastric barostat studies are increasingly being performed, but their reproducibility and the most suitable study protocol have not been determined. The aim of this study was to verify the reproducibility of gastric sensitivity and accommodation testing in healthy and in dyspeptic subjects, and to compare stepwise and double random staircase distensions. METHODS: A total of 13 dyspeptic patients and 25 healthy control subjects underwent two successive studies. Sensory thresholds were assessed on a same-day/different-days protocol, using a stepwise (11/14 healthy subjects and 11/13 patients) or a double random staircase inflation (11/21 healthy subjects). In 10 healthy subjects, both methods were compared. Gastric accommodation was measured on different days in 13 patients and nine healthy subjects. Data (mean +/- SEM) were compared using the paired t test, and individual variability was expressed as the percent coefficient of variation. RESULTS: In healthy subjects, the thresholds for first perception and for discomfort were highly reproducible (p > 0.05) and the pressure thresholds showed a lower degree of variability than the volumes. Pressure thresholds quantified by stepwise showed lower variability than double random staircase inflation. In the patients, the sensory thresholds were unchanged between the sessions on the same and on different days (p > 0.05). Gastric accommodation also showed excellent reproducibility for both dyspeptic patients and healthy control subjects (p > 0.05). CONCLUSIONS: Both in dyspeptic patients and in healthy control subjects, gastric sensitivity and accommodation quantified by isobaric distensions show excellent reproducibility. Pressure and volume thresholds both are well reproducible, but the former shows less variability. Finally, the simplest stepwise protocol is better than the double random staircase to assess the gastric sensitivity to distension.

Adult↗

PubMed2001

Composition of the postprandial refluxate in patients with gastroesophageal reflux disease.

OBJECTIVE: It is not known whether the characteristics of the postprandial refluxate in patients with gastroesophageal reflux disease (GERD) differ from those observed in normal subjects. The aim of this study was to characterize the postprandial refluxate in adult patients with GERD using combined intraluminal electrical impedance and pH measurements. METHODS: Postprandial gastroesophageal reflux was assessed in 16 patients with GERD and 15 controls. pH and intraluminal electrical impedance were used to identify acid and nonacid reflux of liquid, mixed (liquid + gas) or gas. RESULTS: Transient lower esophageal sphincter relaxations (TLESRs) and reflux of gastric contents were equally frequent in both groups. However, patients with GERD had more acid reflux [8 (4.7-10.5)/h vs 3.5 (2.6-6)/h, p < 0.05], and normal subjects had more nonacid reflux [5 (4.3-6.7)/h is 3 (1-3.5)/h, p < 0.05]. Gas reflux was less frequent in GERD than in controls (51% vs 68%; p < 0.05). Pure liquid reflux, however, was more frequent (40% vs 26%, p < 0.05) and twice as likely to be acid in GERD. During TLESRs, liquid acid reflux was more frequent in GERD than in controls. CONCLUSIONS: TLESRs and reflux of gastric contents are similarly frequent in patients with GERD and controls. However, patients with GERD have more acid reflux and less nonacid reflux. Differences in the air-liquid composition of the refluxate may contribute to the higher rate of acid reflux observed in these patients.

Acids↗

PubMed2001

The role of acid and duodenal gastroesophageal reflux in symptomatic GERD.

OBJECTIVE: Mixed reflux of acid and duodenal contents frequently occurs in patients with gastroesophageal reflux disease (GERD). The aim of this study was to establish the contribution of acid and duodenal gastroesophageal reflux (DGER) to symptoms in patients with presumed GERD. METHODS: A total of 72 patients (37 women), mean age 45 yr (+/-2 yr), underwent 24-h ambulatory pH and Bilitec monitoring. Patients pressed a marker button when experiencing typical symptoms. For each symptom episode, minimal pH and maximal bilirubin optical density in a 2- or 4-min interval were calculated. For each patient, the symptom index (SI) and symptom-association probability for acid and for bile reflux were determined. RESULTS: A total of 544 symptom episodes were identified. Using a 2-min interval, 28% were associated with acid reflux, 9% with DGER, and 12% with mixed reflux. No significant difference was found when a 4-min interval was used. A positive SI for acid reflux was present in 21% of the patients and for DGER in 14%. All patients with a positive SI for DGER had also a positive SI for acid reflux. A positive symptom-association probability for acid reflux was present in 22% of the patients, for DGER in 7% of the patients, and for mixed reflux in 10% of the patients. CONCLUSIONS: Symptom episodes in patients with presumed GERD are more related to acid reflux than to DGER. DGER does not play a major role in producing typical esophageal symptoms.

Bilirubin↗

PubMed2001

Perception of changes in wall tension of the proximal stomach in humans.

BACKGROUND: Hypersensitivity to distension of the stomach is a frequent finding in functional dyspepsia. During gastric distension studies both wall tension and elongation are increased. AIM: We wished to distinguish changes in wall tension from changes in elongation in the genesis of perception of mechanical stimuli originating from the proximal stomach in healthy subjects. SUBJECTS AND METHODS: Twenty six volunteers were studied using gastric barostat and antroduodenal manometry. In 14 subjects, stepwise isobaric and isovolumetric distensions were performed before and during erythromycin infusion. In all volunteers, on a separate occasion, phasic contractions of the proximal stomach were detected as intraballoon pressure increases during fixed volume inflation. These contractions were matched with perception changes during two 10 minute periods, before and during administration of erythromycin. RESULTS: Erythromycin significantly lowered the perception and discomfort thresholds during stepwise gastric distension. During fixed volume inflation, erythromycin increased the number and amplitude of fundic contractions and enhanced their perception from 51.1 (7.4)% to 64.0 (4.7)%. The proportion of perception score increases coinciding with fundic contractions increased from 47.3 (0.7)% to 81.5 (0.5)%. The amplitude of correctly identified isolated fundic pressure waves was higher compared with non-identified waves. CONCLUSIONS: These results support the hypothesis that changes in gastric wall tension may be involved in the genesis of symptoms originating from the stomach.

Adult↗

PubMed2001

Determination of carbohydrate-deficient transferrin using capillary zone electrophoresis.

BACKGROUND: Current methods for carbohydrate-deficient transferrin (CDT) often suffer from low precision, complexity, or risk of false positives attributable to genetic variants. In this study, a new capillary zone electrophoresis (CZE) method for CDT was developed. METHODS: CZE was performed on a P/ACE 5000 using fused-silica capillaries [50 microm (i.d.) x 47 cm] and the CEOFIX CDT buffer system with addition of 50 microL of anti-C3c and 10 microL of anti-hemoglobin. Native sera were loaded by high-pressure injection for 3 s, separated at 28 kV over 12 min, and monitored at 214 nm. RESULTS: CDT was completely resolved by differences in migration times (di-trisialotransferrin, 9.86 +/- 0.05 min; monosialotransferrin, 9.72 +/- 0.05 min; asialotransferrin, 9.52 +/- 0.04 min), with a CV of 0.15%. The number of theoretical plates was 312,000 +/- 21,000 for the mono- and 199 000 +/- 6500 for the di-trisialylated transferrin. Genetic CB and CD variants showed prominent peaks with migration times of 10.12 +/- 0.06 and 9.89 +/- 0.03 min, respectively, and the carbohydrate-deficient glycoprotein syndrome could be detected, excluding false-positive results. CZE results (as a percentage; y) correlated with the Axis %CDT TIA (x) values by Deming regression analysis: y = 1.92x - 7.29; r = 0.89. CDT values in 130 healthy nonalcoholics were determined. The 2.5th and 97.5th percentiles were 1.84% and 6.79%. CONCLUSIONS: CZE without sample pretreatment can determine CDT with good precision, allows detection of variants, and correlates with ion-exchange chromatography.

Adult↗

PubMed2000

Transient lower esophageal sphincter relaxations and esophageal body muscular contractile response in reflux esophagitis.

In patients with gastroesophageal reflux disease (GERD), transient lower esophageal sphincter relaxations (TLESRs) are more frequently accompanied by acid reflux than in normals. The role of esophageal tone during gastroesophageal reflux events is unknown. We studied the tonic motor activity in the body of the esophagus during TLESRs with and without acid reflux in 11 patients with erosive esophagitis and compared the results with those previously obtained in healthy subjects. Esophageal peristaltic contractions were recorded 13, 8, and 3 cm above a sleeve that measured LES pressure. An intraluminal balloon was inflated 8 cm above the sleeve to induce an esophageal tonic contraction [artificial high pressure zone (HPZ)]. The percentage of TLESRs with acid reflux was significantly higher in patients with esophagitis than in healthy controls (58.3% vs 37.3%, P < 0.05). TLESRs per se were not associated with an inhibition or increase in esophageal body contractility, which, however, changed substantially immediately after reflux. In patients with esophagitis the esophageal body tonic contractility was inhibited in 59.5% of TLESRs vs 36% in controls (P < 0.05). Esophageal contractions during TLESRs traveled down the esophagus in 77% of the instances in patients vs 96.5% in controls (P < 0.05). In conclusion, gastroesophageal reflux during TLESRs was more frequently associated with inhibition of esophageal body tonic contractility in patients with esophagitis than in normals. The different response of the esophageal body to reflux observed in GERD patients may partially contribute to the higher prevalence of reflux during TLESRs in these patients.

Adult↗

PubMed2000

Analysis of ambulatory duodenogastroesophageal reflux monitoring.

Some methodological in vitro observations concerning bile reflux monitoring (Bilitec) suggested that Bilitec monitoring is underestimating reflux in an acid environment. Moreover, other studies showed that the area above the cutoff level of bilirubin absorbance would provide an adequate quantitative marker for reflux of duodenal contents. Our aim was to study whether correction for intraesophageal acidity and the area above cutoff during Bilitec monitoring affects the results and the correlation with pH measurement and esophageal lesions. In 84 patients (46 men; mean age 46 +/- 2.7 years) evaluated for suspected gastroesophageal reflux disease, we performed ambulatory 24-hr esophageal pH and Bilitec monitoring after an upper gastrointestinal endoscopy. We obtained total area, percent total time, and correction by computer software. The correction factor for bilirubin absorbance was based on literature data for acidified bile (0.06 for pH < 3.6; 0.21 for pH < 2.6). Endoscopy revealed esophagitis grade 1-2 (E1-2) and 3-4 (E3-4) in 23 and 16 patients, respectively. A progressive increase of mixed (acid + bile) reflux occurred with increasing severity of endoscopic lesions (E3-4 vs no esophagitis, P < 0.05). A pathologic Bilitec monitoring result was present in the same 35 patients before and after correction and the correlation between the pH measurement and percent time of bile reflux was not improved by correction for intraesophageal pH (r = 0.386 and r = 0.391; P < 0.05). The total area of bilirubin absorbance above 0.14 (abs x min) was 7.8 +/- 2.2 in patients without esophagitis, and 11.7 +/- 4.4 and 17.0 +/- 4.2 in the E1-2 and E3-4 groups, respectively (E3-4 vs no esophagitis, P < 0.05). The correlation between the Bilitec monitoring and pH measurement regarding percent (r = 0.427, P < 0.01) or area of time below 4 (r = 0.280, P < 0.05) was not improved by considering the area of bilirubin absorbance above the cutoff level. Correction for intraesophageal pH has only a minor effect on the results of ambulatory Bilitec monitoring. Taking into account the surface rather than the percent of time above the cutoff level for bilirubin absorbance does not improve the correlation of Bilitec with acid reflux and with esophageal lesions.

Adolescent↗

PubMed2000

Synaptic transmission induces transient Ca2+ concentration changes in cultured myenteric neurones.

The enteric nervous system controls most of the gastrointestinal functions. We applied confocal microscopy and the Ca2+ indicator Fluo-3 as an optical approach to study synaptic activation in cultures of myenteric neurones. The optical recording of [Ca2+]i (the intracellular Ca2+ concentration) was used to monitor activation, since [Ca2+]i is crucial in the coupling between neuronal excitation and the activation of several intracellular events. Extracellular fibre tract stimulation (2 s, 30 Hz) caused a transient [Ca2+]i rise in a subset of neurones (50%). These transients lasted for 5.2 s (n=36), with an average amplitude of 3.4 +/- 1.3 times the basal concentration. The removal of extracellular Ca2+ (n=15) or the application of 10-6 M tetrodotoxin (n=16) blocked this response. The N-type Ca2+-channel blocker omega-conotoxin (5 x 10 -7M) abolished the [Ca2+]i increase, while blockade of L-type and P/Q type Ca2+ channels had no effect. Single stimuli evoked a [Ca2+]i rise in the processes. omega-conotoxin-sensitive postsynaptic events required repetitive stimulation. Cholinergic blockade did not inhibit the [Ca2+]i rise in all neurones, suggesting that, besides acetylcholine, other neurotransmitters are involved. Optical imaging of [Ca2+]i can be used to study synaptic spread of activation in enteric neuronal circuits expressed in culture.

Action Potentials↗

PubMed2000

IL-1beta and IL-6 excite neurones and suppress cholinergic neurotransmission in the myenteric plexus of the guinea pig.

The effects of the inflammatory mediators interleukin-1beta (IL-1beta) and interleukin-6 (IL-6) on myenteric neurones were investigated by intracellular recordings in a conventional myenteric plexus preparation of guinea pig ileum. Micropressure ejection of IL-1beta and IL-6 (10-7 mol L-1) both caused an excitatory effect in, respectively, 19% (13/70) and 7% (5/70) of the myenteric neurones. The IL-1beta-induced depolarizations were inhibited by superfusion of the IL-1beta receptor antagonist. The responses seen were tetrodotoxin-resistant, indicating a direct neuronal effect. Responses to both cytokines were seen in nitric oxide synthase-immunoreactive as well as choline acetyltransferase-immunoreactive neurones. In addition, both IL-1beta and IL-6 reversibly caused a presynaptic inhibition of acetylcholine release from cholinergic nerve terminals. Both cytokines had no effect on the slow excitatory postsynaptic potentials. Therefore, we can conclude that the inflammatory mediators IL-1beta and IL-6 can act as excitatory neuromodulators of gastrointestinal motility through direct excitatory actions on a subset of myenteric neurones and through the presynaptic inhibition of acetylcholine release.

Animals↗

PubMed2000

Influence of sumatriptan on gastric fundus tone and on the perception of gastric distension in man.

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 effect 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 effect 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 effects of sumatriptan on the gastric fundus may have therapeutic potential in the treatment of patients with functional dyspepsia.

Adult↗