Role of platelet-activating factor (PAF) and prostaglandins in colonic motor and secretory disturbances induced by Escerichia coli endotoxin in conscious rats

Pons, Laurent; Mt, Droy-Lefaix; Buéno, Lionel

doi:10.1016/0090-6980(94)90082-5

Cited by 15 publications

(13 citation statements)

References 31 publications

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“…The intestinal effects of castor oil have been associated with mucosal injury and the release of several endogenous mediators, such as prostaglandins (Pons et al , 1994), PAF (Pinto et al , 1992) and nitric oxide (NO) (Mascolo et al , 1994), but not of tachykinins. We have investigated the role of endogenous tachykinins in castor oil diarrhoea as disclosed by their specific receptor antagonists, SR 140333 and SR 48968.…”

Section: Discussionmentioning

confidence: 99%

Role of tachykinins in castor oil diarrhoea in rats

Croci

Landi

Emonds‐Alt

et al. 1997

British J Pharmacology

102

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1 We set out to ascertain the role of tachykinins, neurokinin A and substance P, in castor oil-induced diarrhoea in rats as disclosed by the inhibitory e ect of the non-peptide NK 1 -and NK 2 -receptor antagonists, SR 140333 and SR 48968, respectively. 2 SR 48968 (0.02 to 20 mg kg 71 , s.c. or p.o.), and the opioid receptor agonist loperamide (1 ± 10 mg kg 71 , p.o.), dose-dependently prevented castor oil e ects: % inhibition vs castor oil, diarrhoea 0 to 100, increase in faecal mass 7 to 90 and water content 16 to 90. SR 140333 (0.02 to 20 mg kg 71 , s.c.) and the platelet activating factor antagonist SR 27417 (5 to 500 mg kg 71 , p.o.) did not prevent the increase in faecal water content, but reduced faecal mass (35 to 66%) and diarrhoea (0 to 57%). 3 The R-enantiomers of tachykinin NK 1 and NK 2 receptor antagonists, SR 140603 and SR 48605 (both at 2 or 20 mg kg 71 , s.c.) had no e ect other than reducing faecal mass at the highest dose tested. 4 SR 48968 (20 mg kg 71 , p.o.) but not loperamide (10 mg kg 71 , p.o.) given 24 h before castor oil, still slightly but signi®cantly reduced by 30% the increase of faecal mass output; both treatments signi®cantly reduced (30 to 70%) the e ect of castor oil on faecal water content, although the incidence of diarrhoea was only slightly less than in controls. 5 In castor oil-treated rats, naloxone (2 mg kg 71 , s.c.) completely blocked the antidiarrhoeal action of loperamide (10 mg kg 71 , p.o.) but not of SR 48968 (20 mg kg 71 , p.o.); a similar result was obtained on faecal mass and water content. 6 Castor oil strongly increased the occurrence of manometrically recorded propulsive giant contractions (500 to 1000% over control values) of transverse and distal colon, this e ect being signi®cantly prevented (80 to 100%) by SR 48968 and loperamide and partially by SR 140333 (35% distal colon, 70% transverse colon). 7 In castor oil free rats, loperamide but not SR 48968 or SR 140333 signi®cantly reduced by 50% the gastrointestinal transit of a charcoal test meal, as well as 24 h faecal mass output. Consistently, loperamide, unlike the tachykinin receptor antagonists, had a dramatic e ect on manometric recordings of intestinal motility, reducing all kinds of colonic contractions. 8 Our ®ndings suggest that castor oil diarrhoea in rats entails activation of NK 1 and NK 2 receptors by endogenous tachykinins, whose antagonists may have a potential as antidiarrhoeal agents free from the constipating action of opioids.

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Section: Discussionmentioning

confidence: 99%

Role of tachykinins in castor oil diarrhoea in rats

Croci

Landi

Emonds‐Alt

et al. 1997

British J Pharmacology

102

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“…In addition, a similar dose of endotoxin has been shown to increase intestinal transit in anaesthetized rats and faecal excretion in conscious rats within one hour of administration [42,85]. The effect of endotoxin on faecal excretion was only observed within the first three hours after challenge and was not associated with changes in the consistency of the faeces, suggesting that the effect of endotoxin was independent of changes in intestinal secretion, in contrast to that reported with slightly higher doses of intravenous endotoxin [84]. Such a prokinetic effect of endotoxin on intestinal motility seems to be mediated by a long nervous reflex, similar to what happens in the stomach, as endotoxin effect on faecal excretion is prevented by subdiaphragmatic vagotomy or systemic pre-treatment with capsaicin [42].…”

Section: Increase Of Intestinal Transitmentioning

confidence: 55%

“…Administration of doses of µg/kg of E. coli endotoxin induce a significant increase of colonic motility and transit in conscious rats, an action that was reported to be partly mediated by PAF and PGs [84]. In addition, a similar dose of endotoxin has been shown to increase intestinal transit in anaesthetized rats and faecal excretion in conscious rats within one hour of administration [42,85].…”

Section: Increase Of Intestinal Transitmentioning

confidence: 97%

Nitrergic Modulation of Gastrointestinal Function During Early Endotoxemia

Quintana

Barrachina²,

Esplugues³

2006

CPD

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After bacterial infection, the host reacts by signalling to the central nervous system where a cascade of physiologic, neuroendocrine and behavioural processes is orchestrated, collectively termed the acute phase response. Endotoxemia following Gram-negative bacterial infection induces a wide array of effects, including fever, loss of appetite and changes in gastrointestinal function that attempt to eliminate the challenge and restore homeostasis. Systemic administration of low doses of endotoxin (5-40 microg/kg) to rats is associated with changes in gastrointestinal motor function, inhibition of gastric acid secretion and increase in the gastric mucosal resistance to damage. These changes are rapid in onset (observed within one hour), not related to vascular dysfunction, and appear to be mediated by mechanisms that involve the peripheral and the central nervous system. Nitric oxide (NO) plays a central role in the physiology of the gastrointestinal tract and its response to illness. Accumulated evidence supports an increase of NO synthesis in the brainstem, as well as in the gastric myenteric plexus thirty minutes after endotoxin administration. Such a synthesis is due to constitutive nitric oxide synthase (NOS) and occurs before the induction of NOS takes place. In this review we provide experimental evidence supporting the hypothesis that activation of a physiologic mechanism, mediated by the autonomic and the central nervous systems as well as constitutive NOS isoforms, is involved in acute changes of gastrointestinal function during early endotoxemia.

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“…In rats, the LPS induced intestinal myoelectrical disturbances are partially PAF dependent (Pons et al , 1991, 1994; Million et al , 1997). In ponies LPS provoked a reduction in gastric motility, which could be antagonized by PAF antagonism (King & Gerring, 1990).…”

Section: Discussionmentioning

confidence: 99%

Involvement of platelet activating factor in the endotoxin‐induced effects on gastrointestinal electrical activity and some haematological parameters in the conscious miniature pig

Wechsung

Houvenaghel

2000

Vet Pharm & Therapeutics

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Involvement of platelet activating factor in the endotoxin-induced effects on gastrointestinal electrical activity and some haematological parameters in the conscious miniature pig Wechsung, E., Houvenaghel, A. Involvement of platelet activating factor in the endotoxin-induced effects on gastrointestinal electrical activity and some haematological parameters in the conscious miniature pig. J. vet. Pharmacol. Therap. 23, 323 -327.In conscious miniature pigs the influence of intravenous dose of lipopolysaccharide (LPS), 10 mg/kg over 10 min, with and without pretreatment with a platelet activating factor (PAF) antagonist, SAH 63-675 10 mg/kg, on gastrointestinal electrical activity, arterial pressure and clinical and haematological parameters was studied. Dose of LPS provoked mild clinical signs and hypotension, which were prevented by PAF antagonism. The LPS induced leukocytosis and increase in mature neutrophils, however, were PAF independent. Pretreatment with the PAF antagonist attenuated the LPS-provoked inhibition of electrical activity in the antrum, jejunum, ileum and caecum. These results suggest a beneficial effect of PAF antagonism in porcine endotoxaemia.(Paper

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Role of platelet-activating factor (PAF) and prostaglandins in colonic motor and secretory disturbances induced by Escerichia coli endotoxin in conscious rats

Cited by 15 publications

References 31 publications

Role of tachykinins in castor oil diarrhoea in rats

Role of tachykinins in castor oil diarrhoea in rats

Nitrergic Modulation of Gastrointestinal Function During Early Endotoxemia

Involvement of platelet activating factor in the endotoxin‐induced effects on gastrointestinal electrical activity and some haematological parameters in the conscious miniature pig

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