A behavioural study of the effect of pentadecapeptide BPC 157 in Parkinson's disease models in mice and gastric lesions induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine

Sikirić, Predrag; Marović, Anton; Matoz, Wendy; Anić, Tomislav; Buljat, Gojko; Mikus, Darko; Stančić-Rokotov, Dinko; Šeparović, Jadranka; Seiwerth, Sven; Grabarević, Željko; Rucman, Rudolf; Petek, Marijan; Ziger, Tomislav; Sebecic, Bozidar; Zoricic, Ivan; Turković, Branko; Aralica, Gorana; Perović, Darko; Duplančić, Božidar; Lovrić-Benčić, Martina; Rotkvić, Ivo; Miše, Stjepan; Jagić, Vjekoslav; Hahn, Vladimir

doi:10.1016/s0928-4257(99)00119-9

Cited by 43 publications

(69 citation statements)

References 40 publications

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“…Our isometric muscle contraction data argue against transient sympathectomy as the sole mechanism of enhanced colon motility, since EFS is primarily an assay of ENS (not PNS) function (Ouyang, et al, 1996), and the electrophysiological abnormalities persisted despite resolution of the behavioral deficit. Alternatively, MPTP has been shown to induce transient gastric and duodenal erosions in rodents, raising the possibility that mucosal injury in the stomach and duodenum may cause a temporary increase in intestinal transit velocity by altering the composition of intestinal contents (Sikiric, et al, 1999, Szabo, et al, 1985.…”

Section: Discussionmentioning

confidence: 99%

Loss of enteric dopaminergic neurons and associated changes in colon motility in an MPTP mouse model of Parkinson's disease

Anderson

Noorian

Taylor

et al. 2007

Experimental Neurology

205

196

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Gastrointestinal (GI) dysfunction is the most common non-motor symptom of Parkinson's disease (PD). Symptoms of GI dysmotility include early satiety and nausea from delayed gastric emptying, bloating from poor small bowel coordination, and constipation and defecatory dysfunction from impaired colonic transit. Understanding the pathophysiology and treatment of these symptoms in PD patients has been hampered by the lack of investigation into GI symptoms and pathology in PD animal models. We report that the prototypical parkinsonian neurotoxin, MPTP (1-methyl 4-phenyl 1,2,3,6-tetrahydropyridine), is a selective dopamine neuron toxin in the enteric nervous system (ENS). When examined 10 days after treatment, there was a 40% reduction of dopamine neurons in the ENS of C57Bl/6 mice administered MPTP (60 mg/kg). There were no differences in the density of cholinergic or nitric oxide neurons. Electrophysiological recording of neural-mediated muscle contraction in isolated colon from MPTP-treated animals confirmed a relaxation defect associated with dopaminergic degeneration. Behaviorally, MPTP induced a transient increase in colon motility, but no changes in gastric emptying or small intestine transit. These results provide the first comprehensive assessment of gastrointestinal pathophysiology in an animal model of PD. They provide insight into the impact of dopaminergic dysfunction on gastrointestinal motility and a benchmark for assessment of other PD model systems.

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Section: Discussionmentioning

confidence: 99%

Loss of enteric dopaminergic neurons and associated changes in colon motility in an MPTP mouse model of Parkinson's disease

Anderson

Noorian

Taylor

et al. 2007

Experimental Neurology

205

196

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“…It may prevent / reverse catalepsy or stereotypy due to central dopamine system failure (33,34). Of note, used in the same dose range, it antagonizes all of the concomitant gastrointestinal lesions, induced by haloperidol (35), reserpine (36), or 1-methyl-4-phenyl-1,2,3,6-tetrahydropropyridine (MPTP) (37).…”

Section: Discussionmentioning

confidence: 99%

Prolonged Esophagitis After Primary Dysfunction of the Pyloric Sphincter in the Rat and Therapeutic Potential of the Gastric Pentadecapeptide BPC 157

et al. 2007

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Abstract. Seven or fourteen days or twelve months after suturing one tube into the pyloric sphincter (removed by peristalsis by the seventh day), rats exhibit prolonged esophagitis with a constantly lowered pressure not only in the pyloric, but also in the lower esophageal sphincter and a failure of both sphincters. Throughout the esophagitis experiment, gastric pentadecapeptide BPC 157 (PL 14736) is given intraperitoneally once a day (10 µg / kg, 10 ng / kg, last application 24 h before assessment), or continuously in drinking water at 0.16 µg / ml, 0.16 ng / ml (12 ml / rat per day), or directly into the stomach 5 min before pressure assessment (a water manometer connected to the drainage port of a Foley catheter implanted into the stomach either through an esophageal or duodenal incision). This treatment alleviates i) the esophagitis (macroscopically and microscopically, at either region or interval), ii) the pressure in the pyloric sphincter, and iii) the pressure in the lower esophageal sphincter (cmH 2 O). In the normal rats it increases lower esophageal sphincter pressure, but decreases the pyloric sphincter pressure. Ranitidine, given using the same protocol (50 mg / kg, intraperitoneally, once daily; 0.83 mg / ml in drinking water; 50 mg / kg directly into the stomach) does not have an effect in either rats with esophagitis or in normal rats.

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“…It may also prevent / reverse catalepsy or stereotypy due to central dopamine system failure (35,36). Of note, all concomitant gastrointestinal lesions, induced by haloperidol (36), reserpine (37), or 1-methyl-4-phenyl-1,2,3,6-tetrahydropropyridine (MPTP) (38), are strongly antagonized with pentadecapeptide BPC 157 used in the same dose-range.…”

Section: Discussionmentioning

confidence: 99%

An Experimental Model of Prolonged Esophagitis With Sphincter Failure in the Rat and the Therapeutic Potential of Gastric Pentadecapeptide BPC 157

et al. 2006

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Abstract. We report a simple novel rat model that combines prolonged esophagitis and parallel sphincters failure. The anti-ulcer gastric pentadecapeptide BPC 157, which was found to be stable in gastric juice, and is being evaluated in inflammatory bowel disease trials, is an antiesophagitis therapy that recovers failed sphincters. Twelve or twenty months after the initial challenge (tubes sutured into sphincters for one week and then spontaneously removed by peristalsis), rats exhibit prolonged esophagitis (confluent hemorrhagic and yellowish lesions, thinner epithelium and superficial corneal layer, with stratification derangement); constantly lowered pressure of both sphincters (assessed by using a water manometer connected to the drainage port of a Foley catheter implanted into the stomach either through esophageal or duodenal incision); and both lower esophageal and pyloric sphincter failure. Throughout the esophagitis experiment, BPC 157 was given at either 10 µg / kg, i.p., once a day (last application 24 h before assessment) or alternatively, it was given continuously in drinking water at 0.16 µg/ ml (12 ml / rat). This treatment recovers i) esophagitis (macroscopically and microscopically, at either region or investigated time period) and ii) pressure in both sphincters (cmH 2 O). In addition, BPC 157 (10 µg / kg) or saline (1 ml / rat, 5 ml / kg) was specifically given directly into the stomach; pressure assessment was performed at 5 min thereafter. The effect of BPC 157 is specific because in normal rats, it increases lower esophageal sphincter-pressure, but decreases pyloric sphincter-pressure. Ranitidine, given as the standard drug using the same protocol (50 mg / kg, i.p., once daily; 0.83 mg / ml in drinking water; or 50 mg / kg directly into the stomach) had no effect.

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A behavioural study of the effect of pentadecapeptide BPC 157 in Parkinson's disease models in mice and gastric lesions induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine

Cited by 43 publications

References 40 publications

Loss of enteric dopaminergic neurons and associated changes in colon motility in an MPTP mouse model of Parkinson's disease

Loss of enteric dopaminergic neurons and associated changes in colon motility in an MPTP mouse model of Parkinson's disease

Prolonged Esophagitis After Primary Dysfunction of the Pyloric Sphincter in the Rat and Therapeutic Potential of the Gastric Pentadecapeptide BPC 157

An Experimental Model of Prolonged Esophagitis With Sphincter Failure in the Rat and the Therapeutic Potential of Gastric Pentadecapeptide BPC 157

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