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J Frexinos

Publications and source records attributed to J Frexinos.

At least 19 recordsLinked to original sources
PubMed1999

The kappa agonist fedotozine relieves hypersensitivity to colonic distention in patients with irritable bowel syndrome.

BACKGROUND & AIMS: Visceral hypersensitivity plays a major role in the pathophysiology of inflammatory bowel syndrome (IBS). Opioid kappa receptors on afferent nerves may modulate it and may be the target of new IBS treatments. The aim of this study was to evaluate the effects of fedotozine, a potent and selective kappa agonist, on responses to colonic distention and colonic compliance in patients with IBS. METHODS: Fourteen patients with IBS (Rome criteria; 50 +/- 12 years; 6 men and 8 women) were included in a randomized double-blind, crossover trial comparing the effect of an intravenous infusion of 100 mg fedotozine or saline on sensory thresholds elicited by left colon phasic distention (4-mm Hg steps for 5 minutes) up to a sensation of abdominal pain. Colonic compliance was compared by the slope of the pressure-volume curves built on placebo and on fedotozine. RESULTS: In the fedotozine group, thresholds of first perception (28.7 +/- 5.9 mm Hg) and pain (34.7 +/- 5.5 mm Hg) were significantly greater than with placebo (23.3 +/- 4.5 and 29.0 +/- 3.5 mm Hg, respectively; P = 0.0078). Colonic compliance was 9. 20 +/- 3.87 mL. mm Hg-1 with placebo and 8.73 +/- 3.18 mL. mm Hg-1 with fedotozine (not significant). CONCLUSIONS: Fedotozine increases thresholds of perception of colonic distention in patients with IBS without modifying colonic compliance. Fedotozine seems capable of reversing visceral hypersensitivity observed in these patients and could have some beneficial action on their symptoms.

Adult↗
PubMed1998

Effect of alosetron on responses to colonic distension in patients with irritable bowel syndrome.

BACKGROUND: Visceral hypersensitivity plays a major role in the pathophysiology of irritable bowel syndrome, as shown by balloon distension studies. 5-HT3 receptors on afferent nerves may modulate visceral sensitivity and be the target of new treatments for irritable bowel syndrome. AIM: To evaluate the effects of alosetron, a potent and selective 5-HT3 antagonist, on the perception of colonic distension by patients with irritable bowel syndrome, and on the colonic compliance to distension with a barostat. METHODS: Twenty-five irritable bowel syndrome patients were included in a randomized double-blind parallel group trial; data were available for 22 (Rome criteria; 48 +/- 11 years: 13 men and nine women). Patients were treated for 7 days with placebo (n = 6), alosetron 0.25 mg b.d. (n = 8) or alosetron 4 mg b.d. (n = 8). On day 6, a barostat bag was placed in the left colon. On day 7, after an overnight fast, isobaric phasic distensions were performed (4 mmHg steps, 5 min) up to the step triggering a sensation of abdominal pain. RESULTS: Groups were comparable at inclusion (age, sex, symptoms, bowel habits). There were no differences between treatment groups in pressure recorded within the bag at the time of first sensation of abdominal pain. However, bag volumes were significantly increased. At the first sensation threshold, median volume differences of 61 mL and 90 mL (P = 0.028) were recorded with alosetron 0.25 mg b.d. and 4 mg b.d., respectively. At the threshold of abdominal pain, these differences were 71 mL (P = 0.039) and 84 mL (P = 0.017). Colonic compliance increased from 5.9 mL/mmHg on placebo to 7.6 mL/mmHg on alosetron 0.25 mg b.d. and to 9.8 mL/mmHg (P = 0.034) on alosetron 4 mg b.d. CONCLUSION: Alosetron increases the compliance of the colon to distension, and could thereby contribute to changes in perception of colonic distension and improvement in the symptoms of irritable bowel syndrome.

Adult↗
PubMed1998

Correlation of desensitisation of platelet activating factor (PAF) receptors with intensity of inflammation and intestinal PAF content during experimental ileitis in guinea pig.

AIM: To determine the kinetics of platelet activating factor (PAF) and prostaglandin E2 (PGE2) receptor desensitisation during intestinal inflammation induced by trinitrobenzenesulphonic acid (TNB) instillation and to study the relation between receptor regulation, inflammatory lesions, and PAF content of the gut wall. METHODS: Receptor desensitisation was assessed on isolated smooth muscle cells from the circular layer. PAF content of the intestinal wall was determined by thin layer chromatography and radioimmunoassay. RESULTS: After an acute inflammatory phase on day 1, subacute changes appeared in TNB instilled ileum, with a maximal intensity on day 6. In control animals, PAF 10 nM and PGE2 10 nM provoked a maximal contraction in the range of 24% of cell shortening. On days 1 and 3 after intestinal instillation of TNB, PAF induced contraction was not altered whereas the effect of PGE2 was progressively desensitised (2 logM rightward shift of its concentration-response curve: Cmax = 1 microM; p < 0.01). Between days 4 and 6, the concentration-response curve of PGE2 shifted by only 1 logM (p < 0.05) whereas the curve of PAF induced contraction shifted by 2 logM (Cmax = 1 microM; p < 0.01). The PAF content of the ileal wall was maximal between days 3 and 5 (300 ng/mg tissue). On days 10 and 15, PAF and PGE2 induced contractions were similar to those observed on day 1, and PAF content returned to basal. CONCLUSION: Inflammation induced by TNB instillation triggers PAF and PGE2 receptor desensitisation; this is dependent on the duration of inflammation and correlates with PAF content in the ileum. This receptor desensitisation may play a protective role by preventing overstimulation of intestinal smooth muscle cells.

Acetylcholine↗
PubMed1998

[Descriptive study of digestive functional symptoms in the French general population].

UNLABELLED: To study the prevalence of "reported" functional digestive symptoms (FDS) in terms easily understood by the general population without resorting to predefined concepts of functional syndromes, and to assess FDS impact on public health, a sample survey has been carried out between September and December 1995. METHODS: Four thousand eight hundred and seventeen subjects representative of the French general population aged 15 years or more filled in a questionnaire describing their digestive disorders. RESULTS: Seventy percent of the subjects had digestive complaints, 9% being related to a presumably organic disease, and 61% attributed to FDS. Twenty-seven % of the subjects claimed to be inconvenienced by their FDS, whereas 34% seemed not to feel any inconvenience. Among FDS, gas emission was the most frequent symptom (59%), followed by stomach ache and/or digestive pain (48%), flatulence (47%), bad digestion sensations (40%), constipation (35%), aerophagia (29%), bad breath (22%), incomplete evacuation of stools (19%). FDS had lasted from 6 months to 5 years in 38%, and over 5 years in 52%. In the subgroup of subjects inconvenienced by FDS (27%), 9% consulted and 18% did not, whereas in the subgroup not inconvenienced, 3% consulted and 31% did not. Altogether, 26% of the subjects followed a prescription or self medication treatment; 35% were not treated. Some explanatory variables appeared to be associated with the onset of inconvenience: the associations pain and bad digestion, flatulence and aerophagia, incomplete evacuation and nervous or presumably organic origin of FDS, age, stress, FDS frequency. Duration of symptoms, age above 65 years, digestive pain, presumably organic origin, and FDS frequency were associated with the need to consult. This descriptive, pragmatic survey shows the widespread prevalence of FDS, affecting 28 million French people. Functional digestive disorders in the "academic" meaning constitute only a limited subset. FDS lead to major health care consumption. Their impact on public health is undoubtedly greater than the estimates derived from studies designed in accordance with conventional nosological categories.

Adolescent↗
PubMed1998

Role of vasoactive intestinal polypeptide in the adaptation of intestinal smooth muscle cells to mechanical distension.

Distension of the small intestine can play a role in the pathogenesis of various functional intestinal disorders. This study determined the role of vasoactive intestinal polypeptide (VIP) in the adaptative response of intestinal smooth muscle to acute and chronic distension of the ileum in vivo. Several in vitro experiments were performed to identify the mechanism of receptor regulation. Distension was applied by a balloon inflated with air in the ileum either during a single episode in anesthetized or repeatedly in conscious guinea pigs. Then, muscle cells were isolated by enzymatic digestion from the distended and nondistended adjacent ileal segments. In addition, in vitro experiments were performed on freshly dispersed cells for determination of mechanisms. Control cells maximally relaxed (Cmax) at 1 microM VIP (EC50 = 50 pM) and 100 microM isoproterenol (EC50 = 7 nM). Both acute and chronic distensions triggered a right-ward shift of the concentration-response curves for VIP (Cmax = 100 microM, EC50 = 10 nM). A desensitization of the relaxing effect of VIP receptors was also observed when cells were preincubated for 30 min in vitro with VIP. By contrast, the relaxing effect of isoproterenol was affected neither by in vivo distension nor by in vitro incubation with isoproterenol. Desensitization of VIP receptors was prevented by in vitro incubation of cells with VIP plus a VIP antagonist [(D-P-Cl-Phe6,Leu17)VIP] and by intraluminal perfusion of the VIP antagonist during acute distention in vivo. Moreover, desensitization of VIP receptors did not occur after 30 min preincubation with either forskolin or 8-Bromo-cyclic AMP. These results indicate that mechanical distension of the ileum induces a homologous desensitization of VIP receptors on circular smooth muscle cells, which requires the occupation of its receptors by VIP.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1997

Mediators and pharmacology of visceral sensitivity: from basic to clinical investigations.

Over the last decade, the role of visceral sensitivity has been largely recognized in the pathophysiology of functional digestive disorders, particularly in the irritable bowel syndrome. These studies have highlighted the role of afferent pathways arising from the gut as a possible target for new treatments intended to relieve pain or modify altered reflexes present in such patients. These pharmacological targets have been identified mainly by studies on animal models of visceral hyperalgesia of various origins including local inflammation. Locally, several mediators are of paramount importance for sensitization of nerve endings: 5-hydroxytryptamine, bradykinin, tachykinins, calcitonin gene-related peptide, and neurotrophins. Selective antagonists to various subtypes of their receptors are currently available and have been shown to be active in these animal models. Other substances, such as somatostatin, opiold peptides, cholecystokinin, oxytocin, and adenosine, modulate the transmission of nociceptive inputs from the gut to the brain and are of clinical interest. This article reviews the current understanding of these mediators. Although these agents seem to be promising tools for the treatment of visceral hyperalgesia and its consequences (abdominal pain and disturbed reflexes), their clinical efficacy remains to be shown. A better understanding of the nature and the location of the defect in the sensory pathways may permit the selection of subgroups of patients for treatment according to the pharmacological properties of these new therapeutic agents.

Animals↗
PubMed1997

The calcitonin gene-related peptide activates both cAMP and NO pathways to induce relaxation of circular smooth muscle cells of guinea-pig ileum.

The direct effects and the intracellular pathways of rCGRP were investigated on smooth muscle cells (SMC) isolated by enzymatic digestion from the circular and longitudinal layers of guinea-pig ileum. In circular SMC, rCGRP inhibited CCK8-induced contraction in a concentration-dependent manner (Cmax = 100 microM and EC50 = 0.7 +/- 0.4 nM). Preincubation of SMC with 1 microM Rp-cAMPs, a cAMP antagonist, abolished the relaxing effect of rCGRP; moreover, preincubation of SMC with 100 microM L-NAME, an inhibitor of NOS, inhibited the relaxing effect of rCGRP, hCGRP(8-37), a selective antagonist of rCGRP receptors, inhibited the rCGRP-induced relaxation in a concentration dependent manner whereas the vasoactive intestinal polypeptide (VIP) antagonist had no significant effect. In longitudinal SMC, rCGRP-induced relaxation was abolished by Rp-cAMPs, whereas L-NAME had no effect. In conclusion, rCGRP triggers different intracellular pathways to induce relaxation of circular or longitudinal intestinal SMC; cAMP is involved in cells from both layers while nitric oxide (NO) is involved only in relaxation of circular SMC.

Animals↗
PubMed1997

Intraduodenal free fatty acids rather than triglycerides are responsible for the release of CCK in humans.

Exocrine pancreas from different species behaves differently in response to the presence of intact or digested nutrients in the duodenum. A failure of cholecystokinin (CCK) release after a meal has been shown among patients with exocrine pancreatic insufficiency. This abnormality could be restored by the administration of pancreatic extracts, suggesting that digested rather than intact nutrients are responsible for the release of CCK and subsequently gallbladder contraction in humans. The aim of this study was to determine the specific role of different lipidic stimuli in humans. Seven male patients (mean age, 52 years) with pancreatic insufficiency secondary to chronic pancreatitis were selected. Pancreatic insufficiency was considered severe in five of them (lipase output, < 1,000 IU/min) and moderate in another two (lipase output, > 1,000 and < 2,300 IU/min). Plasma CCK (by bioassay), gallbladder contraction (by ultrasound), and enzyme output (chymotrypsin) in response to duodenal administration of either oleic acid as free fatty acids or 20% Intralipid as triglycerides were measured in each patient with at least a 48-h interval between each test. In all these patients with pancreatic insufficiency, duodenal perfusion of free fatty acids generated a more pronounced (91 +/- 11 vs. 49 +/- 21 pM) and faster (15 vs. 30 min) (p < 0.05) CCK release than triglycerides. Furthermore, gallbladder contraction was more efficient when free fatty acids instead of triglycerides were administered in the duodenum (86 +/- 5 vs. 69 +/- 4%) at 10 min (p < 0.05) and (73 +/- 8 vs. 51 +/- 5%) at 15 min (p < 0.03). Among patients with measurable residual pancreatic function, enzyme outputs were shown to be higher during free fatty acid than triglyceride perfusion. In humans, free fatty acids rather than triglycerides, when present in the duodenum, stimulate CCK release and gallbladder contraction. In patients with moderate pancreatic insufficiency this phenomenon may increase residual enzymatic secretion. These results allow us to encourage the development of enzymatic preparations as acid-resistant lipases that cause a fast release of free fatty acids in the duodenum.

Adult↗
PubMed1996

Intracolonic injection of glycerol: a model for abdominal pain in irritable bowel syndrome?

BACKGROUND & AIMS: Abdominal pain is the main symptom in patients with irritable bowel syndrome (IBS). Glycerol is an irritant of colonic mucosa. The aim of this study was to evaluate the effects of an intraluminal injection of glycerol on colonic motility and tone in patients with IBS and their modulation by drugs. METHODS: Colonic motility was evaluated using electromyography, and colonic tone was assessed using a barostat. Glycerol was injected in the right colon or the rectum. RESULTS: After intracolonic injection of glycerol, a strong abdominal colic occurred and was associated with an increase in long spike burst activity (+280%), which was eliminated by previous administration of lidocaine and was not observed after paraffin oil. When glycerol was injected intrarectally, abdominal pain occurred and long spike burst activity was increased (+240%) in the left colon. Simultaneously, colonic tone decreased (-70%) and high-amplitude phasic contractions occurred (10 +/- 1/patient). This rectocolonic reflex was reproducible in the same patient. Drugs acting on visceral afferent pathways (octreotide and granisetron) did not modify this reflex, whereas the spasmolytic drug phloroglucinol inhibited phasic contractions without affecting tone. CONCLUSIONS: Intraluminal injection of glycerol triggers viscerovisceral reflexes, resulting in abdominal pain in patients with IBS. It could be used as a model for the study of effects of drugs on pain in these patients.

Abdominal Pain↗
PubMed1996

VIP-induced relaxation of guinea-pig intestinal smooth muscle cells: sequential involvement of cyclic AMP and nitric oxide.

1. A possible interaction between cyclic AMP and nitric oxide (NO) in mediating the relaxant effect of vasoactive intestinal polypeptide (VIP) on intestinal smooth muscle cells has been investigated. The effects of the inhibitor of NO synthesis, NG-nitro-L-arginine methyl ester (L-NAME), have been studied on VIP-, forskolin-, and 8 bromo-cyclic AMP- induced relaxation of cells, dispersed by enzymatic digestion of muscle strips from the circular layer of guinea-pig ileum. 2. VIP alone did not modify the length of isolated muscle cells. By contrast, when the cells were contracted by cholecystokinin octapeptide, CCK8 (10 nM), VIP inhibited this contraction, inducing a concentration-dependent relaxation of the cells. Maximal relaxation was induced by 1 microM VIP (EC50 = 408.2 +/- 16.7 pM). 3. N-ethylmaleimide, inhibitors of adenylate cyclase or somatostatin, abolished the relaxing effect of VIP. (R)-p-cAMPs, an antagonist of cyclic AMP on protein kinase A also inhibited the VIP-induced relaxation by 92.1 +/- 6.3%. Inhibitors of nitric oxide synthase (NOS), L-NAME and L-NMMA, partially inhibited VIP-induced relaxation. The effect of L-NAME was reversed by L-arginine but not by D-arginine. 4. (R)-p-cAMPS and L-NAME also inhibited the cell relaxation induced either by forskolin which directly stimulates adenylate cyclase activity or 8-bromo-cyclic AMP, an analogue of cyclic AMP. 5. When cells were incubated for 30 min with dexamethasone 10 microM, a glucocorticoid known to decrease the synthesis of iNOS, the relaxing effect of a maximal concentration of VIP was decreased by 52 +/- 4% and L-NMMA had no further effect on this residual VIP-induced relaxation. Milrinone, a phosphodiesterase type III inhibitor, potentiated the relaxant effect of VIP. 6. These data demonstrate that the intracellular pathway mediating the relaxant effect of VIP in intestinal smooth muscle cells includes the sequential activation of adenylate cyclase, protein kinase A, activation of NOS and finally production of NO and cyclic GMP. NO could in turn regulate the cyclic AMP-dependent pathway of cell relaxation.

Animals↗
PubMed1996

Oxytocin increases thresholds of colonic visceral perception in patients with irritable bowel syndrome.

AIM: The effects of oxytocin on colonic perception of intraluminal distension were evaluated in 26 patients with irritable bowel syndrome (IBS), using a flaccid bag placed in the descending colon and connected to a computerised barostat. METHOD: Symptomatic responses (first sensation and pain) were evaluated during isobaric distensions (4 mm Hg increments, five minute duration, five minute interval with return to zero pressure between each step), performed automatically by the barostat, during a continuous infusion of placebo or various doses of oxytocin (10, 20, 30, and 50 mU/min). RESULTS: The distension pressure (mean (SD)) required to induce a first abdominal sensation was 17.3 (5.5) mm Hg on placebo, 19.9 (5.8) on oxytocin 10 mU/min (NS), 22.3 (6.0) mm Hg on oxytocin 20 mU/min (p < 0.01), 23.1 (6.6) mm Hg on oxytocin 30 mU/min (p < 0.01), and 24.0 (7.1) mm Hg on oxytocin 50 mU/min (p < 0.01). The distension pressure required to induce pain was 24.8 (6.3) mm Hg on placebo, 26.0 (5.8) on oxytocin 10 mU/min (NS), 33.3 (7.8) mm Hg on oxytocin 20 mU/min (p < 0.01), 34.2 (7.6) mm Hg on oxytocin 30 mU/min (p < 0.01), and 34.3 (7.9) mm Hg on oxytocin 50 mU/ min (p < 0.01). Compliance curves were not different after placebo and oxytocin injection at the different doses. Naloxone did not inhibit the effect of oxytocin. Oxytocin also did not alter somatic perception, characterised by the RIII reflex at the level of the biceps femori. CONCLUSIONS: Oxytocin significantly increases thresholds for visceral perception in IBS patients at doses equal or to greater than 20 mU/min, possibly by acting at the level of visceral afferents.

Adult↗
PubMed1996

[Specific respiratory manifestations associated with hemorrhagic rectocolitis. Analysis of a case and review of the literature].

Respiratory impairments occurring as systemic manifestations of ulcerative colitis are often misinterpreted. We report a case of chronic productive bronchitis associated with ulcerative colitis; symptoms appeared after colectomy. Clinical features distinguished it from common chronic bronchitis: it occurred in a woman without respiratory disease or smoking history, a chronic productive cough without bronchiectasis, negative infectious investigations, severe endoscopic and histologic lesions, and above all remarkable steroid efficacy. Systematic research and early treatment of these manifestations avoids aggravating pulmonary disease, especially secondary bronchiectasis. Though less frequent, other respiratory manifestations of ulcerative colitis have been described, such as asphyxiating tracheal stenosis, pneumonia or interstitial pulmonary diseases, pleurisy or pleuro-pericarditis.

Bronchitis↗
PubMed1995

Galanin contracts and relaxes guinea pig and canine intestinal smooth muscle cells through distinct receptors.

BACKGROUND/AIMS: Galanin induces a contraction or a relaxation of digestive smooth muscle. Receptors mediating these effects have not been pharmacologically characterized. The aim of the study was to evaluate properties of two specific galanin antagonists M15 and M35 on galanin effects on muscle cells. METHODS: Isolated muscle cells were obtained separately from circular and longitudinal layers of guinea pig and dog ileums. Contraction was expressed as percentage decrease in cell length from control. RESULTS: Galanin induced a contraction of cells from guinea pig circular layer (50% effective concentration [EC50], 80 pmol/L) and dog longitudinal layer (EC50, 100 pmol/L). The antagonists inhibited galanin-induced contraction. The most potent was M15 (50% inhibitory concentration [IC50], 80 pmol/L in guinea pig; 90 pmol/L in dog) which was > M35 (IC50, 4 nmol/L in guinea pig; 1 nmol/L in dog). In dog circular layer, galanin inhibited cholecystokinin-induced contraction by relaxing the cells (EC50, 3 pmol/L). The antagonists inhibited this relaxation. The most potent was M35 (IC50, 60 pmol/L) which was > M15 (IC50, 900 pmol/L). CONCLUSIONS: Galanin antagonists M15 and M35 inhibit the contraction and the relaxation induced by galanin with different potency, suggesting the presence of distinct galanin receptors in gastrointestinal tract that each mediates a specific effect.

Animals↗
PubMed1995

Desensitization of platelet-activating factor receptors, induced by inflammation in guinea pig ileal smooth muscle cells.

BACKGROUND/AIMS: Platelet-activating factor (PAF) is involved in the pathophysiology of motility changes induced by intestinal inflammation. The aim of this study was to evaluate a possible desensitization of PAF receptors in guinea pig intestinal smooth muscle cells after experimental inflammation induced by trinitrobenzenesulfonic acid (TNB). METHODS: Saline or TNB (80 mg/kg) was injected in the intestinal lumen, and the animals were killed 6 days later. Smooth muscle cells from the circular layer were isolated, and cell contraction induced by PAF was measured. RESULTS: In cells from saline-treated animals, PAF induced a maximal cell contraction at 10 nmol/L and half-maximal contraction (EC50) was 9 +/- 0.2 pmol/L. After TNB injection, the maximal contraction induced by PAF was observed at 1000 nmol/L and EC50 was 300 +/- 70 pmol/L, indicating a 2 logmol/L right shift of the concentration-response curve of PAF. When animals were treated with the PAF antagonist, 20 mg/kg BN52021, or with 2 mg/kg indomethacin for the 6 days after TNB instillation, the right-sided shift of the concentration-response curve of PAF did not occur. CONCLUSIONS: Desensitization of PAF receptors occurring in intestinal smooth muscle cells after TNB instillation could be mediated in vivo by PAF itself via a prostaglandin-dependent pathway.

Acetylcholine↗
PubMed1995

Weakness of mucosal barrier in portal hypertensive gastropathy of alcoholic cirrhosis. Effects of propranolol and enprostil.

BACKGROUND/AIMS: It has been suggested that the vulnerability of gastric mucosa is increased in patients with cirrhosis as a result of a PGE2 deficiency. Therefore, we evaluated whether PGE2 mucosal generation, and gastric potential difference - a reflection of the gastric mucosal barrier - were correlated to endoscopic features and whether these alterations could be alleviated. METHODS: The potential difference was measured before (basal) and after a stimulation test by aspirin. The serum levels of gastrin and glucagon were also determined. Finally, the effects of a 1-week administration of propranolol or enprostil were tested on potential difference. The endoscopic grade of portal hypertensive gastropathy was assessed according to McCormack et al. The results are presented respectively for controls, patients with mild gastropathy, and patients with severe gastropathy. Comparisons were made using variance or covariance analysis after adjustment with age. RESULTS: Basal potential difference was significantly different between the three groups: -30.6, -28.8, -24.9 mV, p <0.05, respectively. The effects of aspirin administration on potential difference parameters were significantly different between the three groups (irritability index: 35 +/- 25, 92 +/- 98, 114 +/- 74 mV2.min, p <0.05, respectively) when non-responders to aspirin were excluded. PGE2 mucosal generation was significantly increased in both the antrum (9.8, 19.5, 19.7 ng/mg proteins, p<0.05, respectively) and in the corpus (8.1, 14.0, 20.2 ng/mg proteins, p<0.05, respectively). PGE2 generation was not related to potential difference. Glucagon serum levels were related to the grade of gastropathy. A 1-week administration of 160 mg/d long-acting propranolol, 35 micro g/d enprostil or placebo did not significantly modify basal potential difference. CONCLUSIONS: Portal hypertensive gastropathy is characterized by a decreased potential difference proportional to the endoscopic severity. The gastric mucosa of patients with cirrhosis seems to be more susceptible to aspirin than that of healthy subjects. It appears that the role of PGE2 is controversial in portal hypertensive gastropathy. Propranolol and enprostil do not improve this decreased potential difference.

Adrenergic beta-Antagonists↗
PubMed1995

The effects of lintopride, a 5HT-4 antagonist, on oesophageal motility.

AIM: To evaluate the effects of various doses of lintopride, a new 5HT-4 antagonist with moderate 5HT-3 antagonist properties, on oesophageal body and lower oesophageal sphincter (LOS) motility in humans. METHODS: Eight healthy male volunteers, mean age 22 (19-28) years, without any history of digestive disease or chest pain, were randomized to three doses of lintopride (0.1, 0.3 and 0.5 mg/kg i.v.) and a placebo at 1-week intervals in a double-blind, crossover study. Oesophageal motility was recorded continuously for 4 h after each dose, using perfused catheters inserted at the level of the LOS and in the body of the oesophagus, at 5, 10 and 15 cm from the LOS. Peristalsis was studied during 10 wet swallows, at 30-min intervals (T0-T240 min). RESULTS: The LOS basal pressure (23.3 +/- 2.0 cmH2O; mean +/- s.d.) remained stable after dosing with placebo to T240. After lintopride, LOS basal pressure increased significantly vs. placebo (AUC comparison: 0.1 mg/kg, P = 0.036; 0.3 mg/kg, P = 0.027; 0.5 mg/kg, P = 0.052). In contrast, the duration and extent of LOS relaxation after swallowing was not affected by any of the three doses of lintopride. The amplitude of peristaltic waves in the oesophagus increased significantly at T30 after lintopride 0.3 mg/kg (34.5 cmH2O, P = 0.020) and 0.5 mg/kg (32.5 cmH2O, P = 0.027), at T60 after 0.3 mg/kg (48.8 cmH2O, P = 0.0009) and 0.5 mg/kg (29.1 cmH2O, P = 0.029) and at T90 after 0.3 mg/kg (34.5 cmH2O, P = 0.0018). CONCLUSIONS: Lintopride significantly increased the LOS basal tone without affecting LOS physiological relaxation after swallowing. Peristaltic waves were also enhanced by lintopride.

Adult↗
PubMed1995

Iloprost: intracellular Ca(2+)-dependent contractile effect on isolated smooth muscle cells from guinea-pig ileum.

Prostaglandin E2 (PGE2) and iloprost induced a concentration-dependent contraction of smooth muscle cells isolated from the circular layer of guinea-pig ileum. PGE2- and iloprost-induced contractions were inhibited by the selective EP1-receptor antagonist, SC19220 (1-acetyl-2-(8-chloro-10, 11-dihydrodibenz (b,f) (1,4) oxazepine-10-carbonyl)-hydrazine), indicating the involvement of the EP1 subtype of the PGE2 receptor. When cells were incubated for 10 min in the presence of strontium (4 mM L-1), an inhibitor of the release of Ca2+ from intracellular store, the contractile effect of PGE2 and iloprost was inhibited. In contrast, incubation of cells in Ca/2+)-free medium, Ca(2+)-free medium plus EGTA, or in the presence of nifedipine, an organic Ca(2+)-channel blocker, did not alter the PGE2- and iloprost-induced contraction. These observations suggest that the myogenic effect of PGE2 and iloprost on intestinal smooth muscle is dependent on the release of intracellular calcium.

Animals↗