Inhibition Of Intestinal Motility Research Articles

SAT675 GLP-1RA Therapy And Intussusception: A Case Report Of Bowel Telescoping In Anobese Patient After Successful Weight Loss On Therapy

Abstract Disclosure: S. Alqaisi: None. W.R. Doerfler: None. T. Latif: None. A. Bandi: None. Background: Glucagon-like peptide receptor agonists (GLP-1RA) are incretin-based drugs that are now a mainstay in managing type 2 diabetes and obesity, offering added cardiorenal benefits. GLP-1RAs slow gastric emptying and small bowel motility, leading to side effects like constipation, nausea, and diarrhea. Small bowel obstruction (SBO), though not well described in clinical trials, has been reported in observational studies. SBO due to intussusception is a rare condition in adults where one segment of the bowel telescopes into the adjacent segment, potentially causing intestinal ischemia. Although GLP-1RA therapy has not been previously linked to intussusception, we present a patient who developed intussusception while on GLP-1RA therapy for obesity. Case: A 54-year-old female with a history of prediabetes, generalized anxiety disorder, diverticulosis, and total hysterectomy with bilateral salpingo-oophorectomy who was referred for obesity class-I (BMI-33) management considered constitutional given the negative work-up. After an initial weight loss of 40 Ibs with diet and exercise, her success stalled. She was started on medical therapy, initially on orlistat which caused diarrhea, then switched briefly to phentermine-topiramate, that resulted in palpitations and increased anxiety. Hence, liraglutide was initiated, resulting in a further weight loss of 25 Ibs. Three months later, she admitted with left lower quadrant abdominal pain, nausea, vomiting, and diarrhea. Lab tests were unremarkable, and an abdominal CT scan showed an 8.9 cm segment of small bowel intussusception without obstruction. Her symptoms improved after a large episode of emesis and placement of a nasogastric tube. She underwent diagnostic laparoscopy followed by exploratory laparotomy. The entire small bowel length was examined, with no abnormalities found, indicating a transient intussusception. She was discharged on liraglutide. Later, she underwent a follow-up small bowel follow-through that showed normal small bowel features. Liraglutide therapy was discontinued, and she remains symptoms free. Discussion: This case highlights the importance of providers being aware of potential adverse effects, including the rare but serious complication of SBO in patients receiving GLP-1RA therapy. Significant weight and omental fat loss may have led to intussusception in our patient. Thinning of the mesentery and loss of visceral fat oppose less resistance to abdominal peristalsis, increasing the risk of intussusception. While the exact mechanism of GLP-1RA-induced SBO remains unclear, it is postulated that inhibition of intestinal motility may play a role, particularly in patients with pre-existing gastrointestinal neuropathy. Therefore, clinicians should monitor patients for signs of gastrointestinal distress or obstruction and investigate suspected cases promptly for timely management. Presentation: Saturday, June 17, 2023

Evaluation of the antidiarrheal activity of 80% methanol extract and solvent fractions of the leaf of Bersama abyssinica fresen (Melianthaceae) in mice

IntroductionThe use of traditional medicinal plants in the management of diarrhea has long been practiced in Ethiopia. B. abyssinica fresen is one of the plants traditionally used to treat diarrhea whereas an in vivo study had not yet been conducted. Thus, this study aimed to evaluate the antidiarrheal activity of crude extract and solvent fractions of the leaf of B. abyssinica in mice.MethodsCold maceration within 80% methanol was used to extract the leaf powder and extract of the leaf was fractionated using n-hexane, chloroform, and distilled water. The in vivo antidiarrheal activity of crude extracts and solvent fractions were tested in experimental models of castor oil-induced diarrhea, enteropooling, and antimotility test. Five groups each with 6 mice were used under the three antidiarrheal models. Positive controls were treated with loperamide 3 mg/kg and atropine 5 mg/kg and 2% tween 80 was used in the treatment of negative controls. The extract and solvent fractions were administered at doses of 100, 200, and 400 mg/kg. Time of onset of diarrhea, number and weight of total and wet feces, the percent reduction in the number of wet feces, weight and volume of intestinal contents, and percent inhibition of intestinal motility were recorded. Data were analyzed using SPSS version 20.ResultDefecation of castor oil-induced diarrheal or loose stools was inhibited (p < 0.01 to p < 0.001) at 200 mg/kg and 400 mg/kg of crude extract and aqueous fraction. The crude extract and the aqueous fraction at three doses (p < 0.01 to p < 0.001), the chloroform fraction at 200 mg/kg and 400 mg/kg (p < 0.01 to p < 0.001), and the n-hexane fraction at 400 mg/kg (p < 0.05) reduced intraluminal fluid accumulation compared with the negative control. Castor oil-induced intestinal motility was significantly suppressed with the three-doses of aqueous fraction (p < 0.05 to p < 0.001), 200 mg/kg and 400 mg/kg of crude extract (p < 0.05 to p < 0.01), 400 mg/kg of chloroform and n-hexane (p < 0.01 to p < 0.001) compared with negative control.ConclusionThe crude extract, aqueous, and chloroform fractions of B. abyyssinica leaves have promising anti-diarrheal effects, supporting the plant's traditional use to treat diarrhea.

Decrease in the efficacy of glucagon-like peptide-1 receptor agonists: what is the reason?

The review deals with the drugs of a group of glucagon-like peptide-1 receptors agonists (GLP-1RA) the action of which is based on the incretin effect. In addition to insulinotropic and glucagonostatic action, GLP-1RA contributes to the improvement of glycemic control, a decrease in body weight, and also reduces cardiovascular effects in diabetic patients. The members of this group are divided into short- and long-acting preparations that is determined by their pharmacodynamic properties. Studies have shown that the long-acting GLP-1RA, which are administered once a week, demonstrate better glycemic control with a similar or less risk of the hypoglycemia and gastrointestinal side effects than their short-acting analogues. However, with long-term use of GLP-1RA, there is a reduction in the hypoglycemic action associated with a decrease in the inhibition of intestinal motility due to the phenomenon of tachyphylaxis (desensitization) of the GLP-1 receptors as a result of the vagus nerve activation. Promising means to overcome this shortcoming are considered, such as the development of modified and combined coagonists of dipeptidyl peptidase 1 receptors, as well as oral forms of GLP-1RA. In addition, we have described possible mechanisms influencing the effectiveness of GLP-1RA due to the production of antibodies to various drugs in this group, and the relationship between the effects of incretin mimetics with the state of the intestinal microbiota. In conclusion, the group of incretin-based drugs provides broad perspectives for use in type 2 diabetic patients, with the possibility of correction of both basal and prandial glycemia, and new efficient and safe forms of drugs of this group are actively creating.

Toxicological and Pharmacological Activities of Leptohyptis macrostachys (Benth.) Harley and J.F.B.Pastore (Lamiaceae) on Intestinal Smooth Muscle.

Leptohyptis macrostachys, previously known as Hyptis macrostachys Benth., is used in folk medicine to relieve the symptoms of asthma, cough, and bronchitis. Recently, we showed that the ethanol extract obtained from Leptohyptis macrostachys has selective spasmolytic activity on guinea pig ileum. Therefore, the aim of this study was to characterize the spasmolytic mechanism of this extract, investigated whether it presents toxicological and antidiarrheal activities. Therefore, the crude ethanolic extract of Leptohyptis macrostachys was analyzed by high-performance liquid chromatographic-diode array detection (HPLC–DAD). The spasmolytic effect was evaluated on guinea pig ileum, toxicological activity using rats and antidiarrheal activity using male and female mice. In HPLC-DAD analysis, Rosmarinic acid (5.44%) was the most abundant phenolic compound, being considered as a chemical marker. The spasmolytic potency of the extract on histamine-induced contraction was reduced in the presence of 1 mM TEA+, a selective big–conductance K+ channels blocker (BKCa). The extract produces a dose–dependent antidiarrheal activity, inhibiting equipotently defecation frequency and liquid stool formation. In addition, the extract has inhibited in a dose–dependent manner both castor oil–induced intestinal transit and intestinal fluid content. Thus, the spasmolytic activity of the extract involves positive modulation of BKCa and its antidiarrheal activity is related to inhibition of intestinal motility and secretion.

Tachykinin Antagonists Reverse Ischemia/Reperfusion Gastrointestinal Motility Impairment in Rats

BackgroundSupraceliac aortic clamping and unclamping produces ischemia-reperfusion (I/R) injury of the splanchnic organs. The protective effects of tachykinin receptor antagonists, SR140333 (NK1 receptor), SR48968 (NK2 receptor), and SB222200 (NK3 receptor), against I/R-induced inhibition of intestinal motility were tested in rats. Material and methodsThe intestinal transit of Evans blue was measured in untreated rats and animals subjected to skin incision, I/R (1 h superior mesenteric artery occlusion followed by 24 h reperfusion) or sham operation. Surgical procedures were conducted under diethyl ether anesthesia. ResultsThe gastrointestinal transit has not been markedly affected in rats, which were anesthetized or subjected to skin incision in comparison with untreated animals. In contrast, a sham operation and I/R have significantly reduced the intestinal motility. Pretreatment with NK1-3 blockers (SR140333 [3-30 μg/kg]; SR48968 [3-100 μg/kg]; and SB222200 [10-100 μg/kg]) reversed dose dependently the effects of I/R to the level observed after sham operation only. A combination of NK1+NK2+NK3 inhibitors exerted an additive effect compared with NK1 and NK2 antagonists used as single agents. Similarly, combined NK1+NK2 were more effective than NK2 alone. Sham operation and I/R have shifted the in vitro carbachol concentration–response curves to the right in comparison with untreated animals, a phenomenon partially reversed by NK1-NK3 pretreatment. ConclusionsSingle-agent and combined treatment with NK1-3 antagonists markedly attenuated the gastrointestinal dysmotility evoked by I/R injury. The pretreatment with NK3 blocker proved to be the most active in this experimental setting.

PAIN IN NEWBORNS. P ART II. PHARMACOLOGICAL METHODS FOR PAIN RELIEF

For the treatment of pain in patients of all age categories are widely used non-narcotic analgesics, but convincing evidence of efficacy, both non-steroidal anti-inflammatory drugs (NSAIDs) and paracetamol for the relief of pain in newborn does not exist. Antipyretic and analgesic properties of paracetamol and NSAIDs are due to inhibition of cyclooxygenase activity and the inhibition of prostaglandin synthesis. However, acetaminophen differs from NSAIDs absence of anti-inflammatory properties. An additional mechanism of action of paracetamol is the impact of its active metabolites in the endogenous cannabinoid system with a resulting decrease in anxiety, motor activity, muscle tone, decreased body temperature, decreasing symptoms of pain. In addition, the central nociceptive effect of paracetamol is associated with its effects on serotoninergic system and the influence on the transmission of nociceptive signal at the level of spinal cord. When combined with morphine, paracetamol has sparring effect. The toxic effect of paracetamol on liver cells caused by its active metabolites, which depletes the liver from glutathione, and directly damages cells in the liver, which leads to necrosis and cell death, and the subsequent development of liver failure. In newborn activity of enzymes that contribute to the formation of toxic metabolites is decreased, so they rarely develop acetamenophen-induced liver damage. It shows the relationship between the intake of paracetamol in infancy and the risk of asthma or other atopic diseases. The use of narcotic analgesics may be accompanied by respiratory depression, impaired hemodynamic, inhibition of intestinal motility. As the long-term effects of pain in the neonatal period the altered sleep-wake cycles, the development of hyperalgesia and hypersensitivity and cognitive disorders was observed. Both neonatal morphine exposure and repetitive pain have been shown to cause identical disorders: behavioral changes and abnormal learning. It is study the neuroprotective effects of dexmedetomidine, highly selective agonist of α-2 adrenergic receptors, which in combination with narcotic analgesics may minimize anesthetic-induced apoptosis and to reduce the negative influence of narcotic analgesics in the child's developing brain.

OVERVIEW OF NON-TRANSPLANT SURGICAL MANAGEMENT OF SHORT BOWEL SYNDROME IN CHILDREN

The aim of this study was to review the management of Short Bowel Syndrome, focusing on the current trends regarding non-transplant, autologous surgical reconstructive techniques. Management of severe Short Bowel Syndrome is still one of the greatest challenges of medicine. Paediatricians and paediatric surgeons may face this challenge often because of the relatively common occurrence of necrotizing enterocolitis, intestinal malrotation, volvulus, gastroschisis and “apple peel” atresia. Although the short term results of intestinal transplantation are improving, the long term results are still disappointing. On the other hand an increasing number of patients have been saved through modern intestinal bowel rehabilitation programs and autologous intestinal reconstructive surgeries in the last decade. This review summarizes the main medical elements of these programs, such as the control of gastric hypersecretion, inhibition of intestinal motility, elemental enteral feeding, low fat (home) parenteral nutrition and hormonal enhancement of intestinal adaptation. It focuses on nontransplant surgical management of short bowel patients, such as accurate vascular access surgery, controlled bowel expansion program, extracorporeal stool recycling and intestinal lengthening techniques. Conclusion – Intestinal bowel rehabilitation and autologous intestinal reconstruction should be considered as first line management in short bowel patients. The establishment of national bowel rehabilitation centres should be considered. Intestinal transplantation should be reserved for unsuccessful cases and considered as a last resort.

Antidiarrheal Activity of Aqueous Extract of the Stem Bark of &lt;i&gt;Sapium Ellipticum&lt;/i&gt; (Euphorbiaceae)

Purpose: To investigate the antidiarrheal activity of the aqueous extract of the stem bark of S. ellipticum (Euphorbiaceae) (AESE). Methods : AESE was prepared by decoction of the powder from the dry stem bark of S. ellipticum. Its oral antidiarrheal effect was evaluated in vivo at the doses of 5.2, 10.4 and 20.8 mg/kg on castor oil induced diarrhea and on gastro-intestinal transit. AESE was also evaluated in vitro (0.125 – 4 mg/ml) on ileal smooth muscle motility. The acute oral toxicity of AESE (5, 10, 15, 20 and 25 mg/kg) was also assessed in mice. Results: AESE significantly and dose dependently delayed the time of appearance of the first stools, decreased the frequency of defecation and the intestinal transit with respective percentage of 319.14, 62.50 and 36.51 % at the dose of 20.8 mg/kg in comparison with negative control (distilled water). AESE, in a concentration-dependent manner, reduced the tone and amplitude of spontaneous contractions of the ileal smooth muscle with EC50 of 33.29 and 45.43 μg/ml, respectively. None of the doses used in acute toxicity test induced any significant behavioral changes or mortality. Conclusion: These results suggest that AESE possesses antidiarrheal properties mediated at least partially by the inhibition of intestinal motility and may be devoid of acute toxicity. Keywords : Sapium ellipticum , Antidiarrheal, Intestinal transit, Spasmolytic, Acute toxicity.

Deficits in neuronal cytochrome P450 activity attenuate opioid analgesia but not opioid side effects

Morphine-like analgesics act on µ opioid receptors in the CNS to produce highly effective pain relief, but the same class of receptors also mediates non-therapeutic side effects. The analgesic properties of morphine were recently shown to require the activity of a brain neuronal cytochrome P450 epoxygenase, but the significance of this pathway for opioid side effects is unknown. Here we show that brain P450 activity is not required for three of morphine׳s major side effects (respiratory depression, constipation, and locomotor stimulation). Following systemic or intracerebroventricular administration of morphine, transgenic mice with brain neuron – specific reductions in P450 activity showed highly attenuated analgesic responses as compared with wild-type (control) mice. However, brain P450-deficient mice showed normal morphine-induced side effects (respiratory depression, locomotor stimulation, and inhibition of intestinal motility). Pretreatment of control mice with the P450 inhibitor CC12 similarly reduced the analgesia, but not these side effects of morphine. Because activation of brain µ opioid receptors produces both opioid analgesia and opioid side effects, dissociation of the mechanisms for the therapeutic and therapy-limiting effects of opioids has important consequences for the development of analgesics with reduced side effects and/or limited addiction liability.

Inhibition of intestinal motility and secretion by flavonoids in mice and rats: structure-activity relationships.

Intraperitoneal administration of some flavonoids (apigenin, flavone, kaempferol, morin, myricetin, naringin and rutin; 12.5-50 mg kg-1) significantly (P < 0.05-0.01) reduced small (28-69%) and large (83-134%) intestinal transit in mice. Other flavonoids (naringenin, silibinin, silymarin and taxifolin, 100-200 mg kg-1) reduced (23-41%; P < 0.05-0.01) intestinal transit at doses of 100-200 mg kg-1 while hesperitin, catechin and phloridzin (up to 200 mg kg-1) had no effect. This effect was antagonized by yohimbine (87-96%) and phentolamine (87-91%) but not by prazosin, propranolol, atropine, hexamethonium, mepyramine, cyproheptadine and naloxone. Yohimbine (92-96%) also antagonized the inhibitory effect of flavonols (12.5-50 mg kg-1) (P < 0.05-0.01) on intraluminal accumulation of fluid and diarrhoea induced by castor oil. By contrast, verapamil potentiated the flavonol effect. It is suggested that these effects, influenced by the structure of the molecules, are mediated by alpha 2-adrenergic receptors and calcium.

Anti-diarrheal mechanism of the traditional remedy Uzara via reduction of active chloride secretion.

Background and PurposeThe root extract of the African Uzara plant is used in traditional medicine as anti-diarrheal drug. It is known to act via inhibition of intestinal motility, but malabsorptive or antisecretory mechanisms are unknown yet.Experimental ApproachHT-29/B6 cells and human colonic biopsies were studied in Ussing experiments in vitro. Uzara was tested on basal as well as on forskolin- or cholera toxin-induced Cl− secretion by measuring short-circuit current (ISC) and tracer fluxes of 22Na+ and 36Cl−. Para- and transcellular resistances were determined by two-path impedance spectroscopy. Enzymatic activity of the Na+/K+-ATPase and intracellular cAMP levels (ELISA) were measured.Key ResultsIn HT-29/B6 cells, Uzara inhibited forskolin- as well as cholera toxin-induced ISC within 60 minutes indicating reduced active chloride secretion. Similar results were obtained in human colonic biopsies pre-stimulated with forskolin. In HT-29/B6, the effect of Uzara on the forskolin-induced ISC was time- and dose-dependent. Analyses of the cellular mechanisms of this Uzara effect revealed inhibition of the Na+/K+-ATPase, a decrease in forskolin-induced cAMP production and a decrease in paracellular resistance. Tracer flux experiments indicate that the dominant effect is the inhibition of the Na+/K+-ATPase.Conclusion and ImplicationsUzara exerts anti-diarrheal effects via inhibition of active chloride secretion. This inhibition is mainly due to an inhibition of the Na+/K+-ATPase and to a lesser extent to a decrease in intracellular cAMP responses and paracellular resistance. The results imply that Uzara is suitable for treating acute secretory diarrhea.

Inhibition of intestinal motility by the putative BKCa channel opener LDD175

LDD175 (4-chloro-7-trifluoromethyl-10H-benzo[4,5]furo[3,2-b]indole-1-carboxylic acid) is a benzofuroindole compound characterized previously as a potent opener of the large conductance calcium activated (BK(Ca)) channels. Activators of the BK(Ca) channels are potential therapies for smooth muscle hyperactivity disorders. The present study investigates the influence of LDD175 on the mechanical activity of the ileum smooth muscle. LDD175 inhibited spontaneous contractions of the ileum in a concentration-dependent manner (pEC(50)=5.9 +/- 0.1) (E (max)=96 +/- 1.0% at 100 muM, n=3). It also remarkably inhibited contractions due to acetylcholine (ACh) (pEC(50)=5.3 +/- 0.1)(E (max)=97.7 +/- 2.3%, n=6) and electrical field stimulation (EFS) (pEC(50)=5.5 +/- 0.1) (E (max)=83.3 +/- 6.0%, n=6). In strips precontracted by 20 mM KCl, LDD175 significantly reduced the contractions yielding a pEC(50) of 6.1 +/- 0.1 and E (max) of 96.6 +/- 0.9%, (n=6). In 60 mM KCl, a concentration-dependent inhibition was observed with respective pEC(50) and E (max) values of 4.1 +/- 0.1 and 50.8 +/- 5.0% (n=3). BK(Ca) channel blockers iberiotoxin (IbTX) and tetraethylammonium chloride (TEA, 1 mM) attenuated the relaxative effect of LDD175 but not barium chloride (BaCl(2)), and glibenclamide (K(IR) and K(ATP) channel blockers, respectively). These data demonstrate the antispasmodic activity of LDD175 attributable to the potentiation of the BK(Ca) channels.

Role of Peptide YY in Intestinal and Gallbladder Motility in Dogs

The purpose of this study was to characterize the action of exogenous PYY, an ileocolonic peptide released by fatty meal, and that released by Heal perfusion with oleate on intestinal and gallbladder motility patterns and the posssible role of the adrenergic pathway in this action. Dogs were equipped with chronic duodenal electrodes for recording myoelectric activity and with a cannula in the gallbladder fundus for measuring the gallbladders intraluminal pressure and volume and calculating its motility index (MI) and emptying rate. After intravenous infusion of PYY, there was a dose-dependent prolongation of the migrating motor complex (MMC) interval and almost complete abolition of the contractions and emptying of gallbladder during the duodenal activity front. After meat feeding or during intravenous infusion of cerulein, 50 pmol/(kg · h), the MMC was interrupted and replaced by irregular spike activity, accompanied by a marked increase in the gallbladder MI and about 80% to 90% reduction of its volume. PYY, 200 pmol/(kg · h), reduced significantly the meal- or cerulein-induced duodenal spike activity but failed to affect the MI and volume of the gallbladder. Similar changes in fasted and fed patterns of motility were observed after Heal oleate (16 mM/h), producing plasma PYY levels in a range similar to that observed after infusion of exogenous PYY. The inhibitory effects of PYY or Heal fat on intestinal myoelectric activity were reversed in part by α-adrenergic blockade (phentolamine). We conclude that exogenous PYY or endogenous hormone released by Heal oleate inhibits the interdigestive and postprandial motility pattern of the small bowel but does not affect gallbladder motility, and that the inhibition of intestinal motility involves, at least in part, the adrenergic pathway.

Endothelin receptor blockers protect against ischemia/reperfusion impairment of gastrointestinal motility in rats

Intestinal ischemia/reperfusion (I/R) injury remains associated with high morbidity and mortality. The protective efficacy of the following endothelin (ET) receptor blockers: BQ-123 (ET A receptor), BQ-788 (ET B); tezosentan (dual ET blocker) was tested against the inhibition of gastrointestinal (GI) motility induced by intestinal I/R. Intestinal Evans blue transit was measured in untreated (UN) rats and animals subjected to skin incision (SI), I/R (1 h superior mesenteric artery clamping followed by 2–24 h reperfusion) or sham operation (SO). Surgical procedures were conducted under diethyl ether anesthesia. Anesthesia and SI did not affect the GI transit compared to UN rats. In contrast both SO and I/R significantly reduced GI motility, the latter evident at 2–24 h of reperfusion. Tezosentan (1–10 mg/kg), BQ-123 and BQ-788 (0.1–1 mg/kg) protected against I/R-induced inhibition of intestinal motility in a time- and dose-dependent manner at the early and late stages of reperfusion. Furthermore tezosentan alleviated the I/R-induced decrease in the contractile response of the longitudinal jejunal smooth muscle strips to carbachol in vitro. The serum ET(1–21) level was increased at 2 h but not 24 h of reperfusion compared to SO animals and ET(1–21) was higher in tezosentan pretreated rats.

Inhibition of intestinal motility and secretion by extracts of Epilobium spp. in mice

Ethanol extracts of the fresh aerial parts of various Epilobium species were tested to elucidate the mechanism of their gastrointestinal activity in animals. The methods of charcoal meal, castor oil-induced diarrhoea, and enteropooling assay were used to evaluate their effect on mouse gut at various dose levels. The extracts were found to have a significant activity in all models. Moreover, the extracts resulted to possess very little toxicity. Thus, it can be concluded that Epilobium possesses anti-diarrhoeal, anti-motility, and anti-secretory activities and can prove beneficial in the treatment of gastrointestinal disorders.

Somatostatin receptors and regulation of cell proliferation

Somatostatin is an inhibitory neuropeptide, which acts on various targets throughout the body to regulate a variety of physiological functions including inhibition of endocrine and exocrine secretions, modulation of neurotransmission, motor and cognitive functions, inhibition of intestinal motility, absorption of nutrients and ions, vascular contractility and inhibition of normal and tumour cell proliferation. It exerts its effects through interaction with five somatostatin receptors (sst1–sst5), which belong to the family of G-protein-coupled receptors with seven transmembrane spanning domains and are variably expressed in a variety of tumours such as gastroenteropancreatic tumours, pituitary tumours, and carcinoid tumours. This review covers the present knowledge regarding the molecular mechanisms involved in somatostatin antineoplastic activity. Evidence that sst2 receptor acts as a tumour suppressor is also discussed.

Slowing of intestinal transit by PYY depends on an adrenergic pathway

BACKGROUND: Intestinal transit is slowed by peptide YY (PYY) (Gut 28:166,1987). Although reflex inhibition of intestinal motility is known to depend on an adrenergic efferent pathway from the prevertebral ganglia (J Neurophysiol 7:163,1944), it is unknown whether the slowing of intestinal transit by PYY also involves this pathway. To test the hypothesis that the slowing of intestinal transit by PYY depends on an adrenergic pathway, we compared intestinal transit during buffer perfusion of the proximal and distal gut in the absence and presence of the beta-adrenergic blocker, propranolol. METHODS: Four dogs were equipped with duodenal (10 cm from the pylorus) and midgut (160 cm from the pylorus) fistulas. Using occluding Foley catheters, the small intestine was compartmentalized into the proximal (between fistulas) and distal (beyond midgut fistula) one-half of gut. Buffer (pH 7.0) was perfused into both the proximal and distal gut at 2 ml/min for 90 min. PYY was delivered intravenously at 0.8 pg/ kg/h over 90 min, while 50 pg/kg/h propranolol (Prop) or 0.15 M NaCI was delivered intravenously. Intestinal transit across the proximal gut (mean _+ SE) was measured by the recovery of 99m-Tc-DTPA in the output of the midgnt fistula during the last 30 rain of the 90 min experiment. The cumulative % marker (mean -+ SE) recovered was compared using 1-way ANOVA with additional analysis by paired t-tast. RESULTS: 1.Intestinal transit depended on test conditions (p < 0.0005). 2.Intestinal transit was slowed by PYY so that marker recovery was reduced from 74.9 _+ 4.4% (control)to 15.3 _+ 6.3% (PYY)(p < 0.0005). 3.Tho slowing of intestinal transit by PYY was reversed by propranolol, so that marker recovery increased from 15.3 _+ 6.3% (PYY) to 72.2 + 4.8% (PYY + Prop) (p < 0.005). CONCLUSION: The slowing of intestinal transit by PYY depends on a propranolol-sensitive, adranergic pathway.

Role of galanin receptor 1 in the galanin-induced inhibition of intestinal motility

Role of galanin receptor 1 in the galanin-induced inhibition of intestinal motility

The effect of sennosides on bacterial translocation and survival in a model of acute hemorrhagic pancreatitis.

Bacterial translocation leading to subsequent infectious complications is a significant determinant of outcome in acute hemorrhagic pancreatitis (AHP). The colonic ileus and impaired intestinal barrier function that often accompany AHP may predispose to translocation. Sennoside is a naturally occurring cathartic and choleretic agent that stimulates intestinal mucous secretion and has potent promotility effects. The impact of sennoside-induced intestinal motility and secretory function on bacterial translocation and survival was studied in a rat model of AHP. Severe acute pancreatitis was induced in rats by the intraductal infusion of 2% sodium deoxycholate (DCA, 0.4 ml/kg). A group of sham-operated rats (group A) received intraductal saline, whereas experimental animals were subsequently administered distilled water (group B) or sennoside solution (group C) by gavage every 8 h. After 48 h, intestinal transit of fluorescein isothiocyanate-labeled dextran, serum endotoxin, and amylase levels, and bacterial translocation to mesenteric lymph nodes (MLNs) and pancreatic tissue were determined. The pancreas and intestine were sampled for histologic study. All group A animals survived and did not develop pancreatitis or endotoxemia, whereas groups B and C all demonstrated severe hemorrhagic pancreatitis with evidence of necrosis. Mortality at 48 h was 55% in group B versus 12.5% in group C. Inhibition of intestinal motility was noted in 40% versus 20%, and endotoxin levels were 61.36+/-28.26 pg/L versus 5.41+/-3.58 pg/L in group B versus group C rats, respectively (p<0.001). Pancreatic tissue and MLN cultures were positive in 100% of group B survivors versus 14% of group C survivors (p<0.05). Histologic examination of the intestine in group C animals showed increased mucous secretion, proliferation of goblet cells, and evidence of rapid turnover/renewal of enterocytes. Treatment with the cathartic agent, sennoside, reduced translocation of endotoxin and bacteria, restored intestinal motility, increased mucous secretion, and reduced mortality in a model of acute hemorrhagic pancreatitis in the rat. Other cathartics may have similar properties and may be useful in preventing infectious complications in acute pancreatitis.

Experimental evaluation ofMyracrodruon urundeuva bark extract for antidiarrhoeal activity

The bark of M. urundeuva (Anacardiaceae) used in popular medicine as an antidiarrhoeal agent has been investigated for its effects on castor oil-induced diarrhoea and on intestinal motility. In rats, the ethanol extract of stem bark significantly inhibited the castor oil-induced diarrhoea, small intestinal transit and accumulation of fluid volume at an oral dose of 400mg/kg. Furthermore, the plant extract caused marked inhibition of the contractile responses evoked by acetylcholine and histamine on guinea-pig ileum in vitro. These results point to a possible antidiarrhoeic effect of M. urundeuva bark extract since inhibition of intestinal motility and secretion can greatly control clinical diarrhoea.