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Neural contractions in colonic strips from patients with diverticular disease: role of endocannabinoids and substance P.

ABSTRACT: Diverticulosis is a common disease of not completely defined pathogenesis. Motor abnormalities of the intestinal wall have been frequently described but very little is known about their mechanisms. We investigated in vitro the neural response of colonic longitudinal muscle strips from patients undergoing surgery for complicated diverticular disease (diverticulitis).The neural contractile response to electrical field stimulation of longitudinal muscle strips from the colon of patients undergoing surgery for colonic cancer or diverticulitis was challenged by different receptor agonists and antagonists.Contractions of colonic strips from healthy controls and diverticulitis specimens were abolished by atropine. The beta adrenergic agonist (-) isoprenaline and the tachykinin NK1 receptor antagonist SR140333 had similar potency in reducing the electrical twitch response in controls and diseased tissues, while the cannabinoid receptor agonist (+)WIN 55,212-2 was 100 times more potent in inhibiting contractions in controls (IC50 42 nmol/l) than in diverticulitis strips. SR141716, a selective antagonist of the cannabinoid CB1 receptor, had no intrinsic activity in control preparations but potentiated the neural twitch in diseased tissues by up to 196% in a concentration dependent manner. SR141716 inhibited (+)WIN 55,212-2 induced relaxation in control strips but had no efficacy on (+)WIN 55,212-2 responses in strips from diverticular disease patients. Colonic levels of the endogenous ligand of cannabinoid and vanilloid TRPV1 receptors anandamide were more than twice those of control tissues (54 v 27 pmol/g tissue). The axonal conduction blocker tetrodotoxin had opposite effects in the two preparations, completely inhibiting the contractions of control strips but potentiating those in diverticular preparations, an effect selectively inhibited by SR140333.Neural control of colon motility is profoundly altered in patients with diverticulitis. Their raised levels of anandamide, apparent desensitisation of the presynaptic neural cannabinoid CB1 receptor, and the SR141716 induced intrinsic response, suggest that endocannabinoids may be involved in the pathophysiology of complications of colonic diverticular disease.

SUBMITTER: Guagnini F

PROVIDER: S-EPMC1856307 | biostudies-literature | 2006 Jul

REPOSITORIES: biostudies-literature

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Neural contractions in colonic strips from patients with diverticular disease: role of endocannabinoids and substance P.

Guagnini F F Valenti M M Mukenge S S Matias I I Bianchetti A A Di Palo S S Ferla G G Di Marzo V V Croci T T

Gut 20060119 7

<h4>Background and aims</h4>Diverticulosis is a common disease of not completely defined pathogenesis. Motor abnormalities of the intestinal wall have been frequently described but very little is known about their mechanisms. We investigated in vitro the neural response of colonic longitudinal muscle strips from patients undergoing surgery for complicated diverticular disease (diverticulitis).<h4>Methods</h4>The neural contractile response to electrical field stimulation of longitudinal muscle s ...[more]

PMID: 16423891

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Project description:OBJECTIVE:We evaluated the characteristics of patients with diverticular bleeding in whom emergency endoscopy should be proactively performed and those in whom it is unnecessary for spontaneous hemostasis following conservative treatment. METHODS:This study involved 132 patients in whom diverticular bleeding was diagnosed on lower gastrointestinal endoscopy. We evaluated the rate of identification of the bleeding diverticulum during endoscopy and the rate of spontaneous hemostasis following conservative treatment. RESULTS:In 26 patients (20%), bleeding diverticulum was identified during endoscopy. Extravasation or fluid collection on CT imaging was an important factor of successful identification of the bleeding source on endoscopy. Of the 104 patients in the conservative treatment group, 91 (87%) were able to be discharged after spontaneous hemostasis. Univariate analysis revealed a high rate of spontaneous hemostasis in patients without extravasation and fluid collection on CT imaging, those without adhesion of blood during endoscopy, those without diabetes, and those with a hemoglobin level ≥10 g/dL. CONCLUSION:In patients with colonic diverticular bleeding, extravasation or fluid collection on CT is an important factor related to the identification of the bleeding diverticulum. Patients without characteristic CT findings had a high rate of spontaneous hemostasis after conservative treatment. BACKGROUND:Diverticular bleeding is the most frequent cause of lower gastrointestinal bleeding accounting for 20%-40% of all cases in Japan and 20%-48% of all those in the Western countries[1, 2]. The prevalence of colonic diverticula tends to increase with age; thus, the overall prevalence of diverticular bleeding is expected to increase in the future. In Japan, the Japanese Gastroenterological Association published guidelines on colonic diverticulitis in 2017; these guidelines recommend the performance of lower gastrointestinal endoscopic examination within 24 h in patients with lower gastrointestinal bleeding suspected to be diverticular bleeding[3]. It has been reported that, for patients with lower gastrointestinal bleeding, urgent endoscopy helps avoid embolotherapy, colectomy, massive blood transfusion, and repeat bleeding[1, 4, 5]. However, it is often difficult to identify the bleeding point [6]; further, there are many challenging cases wherein it is difficult to decide whether urgent endoscopy should be performed in situations where there is insufficient medical staff, such as during nighttime and on holidays. Bleeding is reported to stop spontaneously with conservative treatment alone in 70% of diverticular bleeding cases[7, 8]. In particular, when determining the treatment policy for diverticular bleeding and in the case of patients at high risk of complications following endoscopy, such as older patients, those with poor performance status or cardiovascular disease, and those in whom spontaneous hemostasis can be expected, urgent endoscopy should be avoided, and elective endoscopy should be selected. Therefore, the type of cases wherein urgent endoscopy is effective and the type wherein it is unnecessary need to be clarified. Thus far, there have been very few reports of the characteristics of patients with diverticular bleeding in whom spontaneous hemostasis was achieved. We aimed to assess the characteristics of patients in whom emergency endoscopy should be proactively performed and those for whom it is unnecessary. Thus, we retrospectively analyzed the identification rate for the responsible diverticulum in patients with diverticular bleeding and the rate of spontaneous hemostasis following conservative treatment.

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Neural contractions in colonic strips from patients with diverticular disease: role of endocannabinoids and substance P.

Publications

Neural contractions in colonic strips from patients with diverticular disease: role of endocannabinoids and substance P.

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