Effects of nematode infection on sensitivity to intestinal distension: Role of tachykinin NK2 receptors

McLean, Peter G.; Picard, Céline; Garcia‐Villar, R.; Moré, J.; Fioramonti, Jean; Buéno, Lionel

doi:10.1016/s0014-2999(97)01275-2

Cited by 66 publications

(63 citation statements)

References 17 publications

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“…Mast cell recruitment was not involved in the clearance of infection, as reported by others in Cryptosporidium-infected infant mice (24). A similar increase in the number of jejunal mucosal mast cells was reported in association with jejunal hypersensitivity in rats infected with Nippostrongylus brasiliensis (18,33,34). A link between postinfectious increase in jejunal mast cells and jejunal hypersensitivity was also supported by the concomitant hypersensitivity to colorectal distension and the increase of mucosal mast cell density observed in adults in a neonatal maternal deprivation rat model (10).…”

Section: Discussionsupporting

confidence: 68%

Cryptosporidium parvumIsolate-Dependent Postinfectious Jejunal Hypersensitivity and Mast Cell Accumulation in an Immunocompetent Rat Model

et al. 2009

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Cryptosporidium spp. are a cause of self-limited diarrhea in immunocompetent hosts. In immunocompetent rats, Cryptosporidium parvum infection induced digestive hypersensitivity, a key pathophysiological factor in functional digestive disorders such as irritable bowel syndrome (IBS). In such a rat model, we sought to document whether jejunal hypersensitivity depends on C. parvum isolate and is associated with a mast cell accumulation. Five-day-old rats were orally administered 10 5 oocysts of either Nouzilly (NoI) or Iowa (IoI) C. parvum isolate. NoI-infected rats exhibited the lowest food intake on days 7 and 14 postinfection (p.i.). On day 7 p.i., small intestine villus atrophy, crypt hyperplasia, and inflammatory cell infiltration were prominent in NoI-infected rats, with higher numbers of Cryptosporidium forms than in IoI-infected rats. Compared to uninfected control rats, jejunal intraepithelial lymphocytes (IELs) were increased only in NoI-infected rats on day 14 p.i. On day 50 p.i., jejunal hypersensitivity to distension was found only in NoI-infected rats; this hypersensitivity is associated with activated mast cell accumulation. The number of mast cells in the jejunal lamina propria was increased from day 36 p.i. in NoI-infected rats and only at day 120 p.i. in IoI-infected rats. Our data suggest that both the severity of infection (weight loss, reduced food intake, villus atrophy, and IEL accumulation) and the onset of a jejunal hypersensitivity after infection in association with an activated mast cell accumulation are isolate dependent and related to NoI infection. This cryptosporidiosis rat model is a relevant model for the study of underlying mechanisms of postinfectious IBS-like symptoms.

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Section: Discussionsupporting

confidence: 68%

Cryptosporidium parvumIsolate-Dependent Postinfectious Jejunal Hypersensitivity and Mast Cell Accumulation in an Immunocompetent Rat Model

et al. 2009

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“…In this model, TAK-480 dose-dependently and significantly inhibited VMR to CRD in accordance with its in vivo NK 2 -receptor antagonism, which was confirmed in an agonist-induced colonic contraction model. This finding suggests the important contribution of the NK 2 receptor in the rabbit model of zymosan-induced visceral hypersensitivity, consistent with data from several rodent models of visceral hypersensitivity (15,16,26). In addition, the maximum inhibition rate of TAK-480 to VMR was comparable to that of the μ-opioid receptor partial agonist buprenorphine and NK 1 -receptor antagonist TAK-637, as demonstrated in our previous reports (approximately, up to 50% inhibition; ref.…”

Section: Discussionsupporting

confidence: 91%

Effects of TAK-480, a Novel Tachykinin NK2^|^ndash;Receptor Antagonist, on Visceral Hypersensitivity in Rabbits and Ricinoleic Acid^|^ndash;Induced Defecation in Guinea Pigs

Tanaka¹,

Tanaka²,

Nakamura³

et al. 2012

J Pharmacol Sci

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Abstract. TAK-480, 4-(difluoromethoxy)-N-((1R,2S)-2-(((3aR,4R,9bR)-4-(methoxymethyl)-2, 3,3a,4,5,9b-hexahydro-1H-pyrrolo[3,2-c]quinolin-1-yl)carbonyl)cyclohexyl)benzamide, is a novel tachykinin NK 2 -receptor antagonist. In this study, we investigated its antagonistic activity and efficacy in animal models of visceral hypersensitivity and stimulated bowel function which have been implicated to underlie the symptoms in irritable bowel syndrome (IBS). TAK-480 showed potent binding affinity for human NK 2 receptors with a marked species difference and a 10,000-fold selectivity versus NK 1 and NK 3 receptors. TAK-480 dose-dependently antagonized colonic contractions induced by administration of the NK 2 receptor-selective agonist beta-Ala 8 -NKA(4-10) (βA-NKA) in anesthetized rabbits. In a rabbit model of intracolonic zymosan-induced visceral hypersensitivity, TAK-480 markedly inhibited the visceromotor response to colorectal distension, in contrast to the moderate inhibition by the serotonin 5-HT 3 -receptor antagonist alosetron. In addition, TAK-480 suppressed ricinoleic acid-induced defecation without affecting spontaneous defecation in guinea pigs, whereas alosetron suppressed both. Furthermore, TAK-480 inhibited smooth muscle contractions produced by natural tachykinins (substance P, neurokinin A, and neurokinin B) as well as βA-NKA in an isolated human colon. In conclusion, the novel NK 2 -receptor antagonist TAK-480 improved visceral hypersensitivity and accelerated defecation without causing constipation in experimental animals. Furthermore, the potent functional blockade of NK 2 receptors in human colon might suggest the potential effectiveness of TAK-480 in IBS patients.

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“…rats. Similar findings were reported for rats previously infected with Nippostrongylus brasiliensis (14). Increase in jejunal, not rectal, sensitivity suggests that it was restricted to the preferred site, i.e., small bowel, of C. parvum infection (16).…”

supporting

confidence: 83%

“…Balloons were arterial embolectomy catheters (Fogarty-Edwards Life Sciences, SaintPrex, Switzerland). Distending the jejunum or rectum by rapid inflation (0.1 to 0.4 and 0.4 to 1.2 ml, respectively; 25 s every 5 min) resulted in a stimulus-related decrease in systemic blood pressure, which was recorded from a side arm of the carotid cannula using a pressure transducer (P10EZ) connected to a window graph 240 (Gould, Courtaboeuf, France) (14).…”

mentioning

confidence: 99%

Transient Neonatal Cryptosporidium parvum Infection Triggers Long-Term Jejunal Hypersensitivity to Distension in Immunocompetent Rats

et al. 2006

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In 5-day-old immunocompetent Sprague-Dawley rats infected with either 10 2 or 10 5 Cryptosporidium parvum oocysts, transient infection resulted 120 days later in increased cardiovascular depressor response to jejunal distension and jejunal myeloperoxidase activity (P < 0.05). Nitazoxanide treatment normalized jejunal sensitivity (P < 0.001) but not myeloperoxidase levels (P > 0.05). Data warrant further evaluation of the role of early cryptosporidiosis in the development of chronic inflammatory gut conditions.

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Effects of nematode infection on sensitivity to intestinal distension: Role of tachykinin NK2 receptors

Cited by 66 publications

References 17 publications

Cryptosporidium parvumIsolate-Dependent Postinfectious Jejunal Hypersensitivity and Mast Cell Accumulation in an Immunocompetent Rat Model

Cryptosporidium parvumIsolate-Dependent Postinfectious Jejunal Hypersensitivity and Mast Cell Accumulation in an Immunocompetent Rat Model

Effects of TAK-480, a Novel Tachykinin NK2^|^ndash;Receptor Antagonist, on Visceral Hypersensitivity in Rabbits and Ricinoleic Acid^|^ndash;Induced Defecation in Guinea Pigs

Transient Neonatal Cryptosporidium parvum Infection Triggers Long-Term Jejunal Hypersensitivity to Distension in Immunocompetent Rats

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