The inhibitory effects of α<sub>2</sub>‐adrenoceptor agonists on gastrointestinal transit during croton oil‐induced intestinal inflammation

Pol, Olga; Valle, Lluı́s; Ferrer, Isidre; Puig, Margarita M.

doi:10.1111/j.1476-5381.1996.tb16085.x

Cited by 15 publications

(15 citation statements)

References 28 publications

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Section: Discussionmentioning

confidence: 99%

“…Croton oil is a well known irritant that has been widely used to produce experimental inflammation in different tissues, especially skin and mucosa, and induces diarrhoea associated with intestinal inflammation in the mouse small intestine (Pol et al ., 1996). According to Pol et al ., (1996), we have shown that croton oil increases upper gastrointestinal transit 3 h after oral administration. The cannabinoid agonists WIN 55,212‐2 and cannabinol blocked the increase in intestinal motility induced by croton oil; in addition, the ED 50 values of i.p.‐injected WIN 55,212‐2 and cannabinol were significantly decreased (compared to control mice).…”

Section: Discussionmentioning

confidence: 99%

“…Gastrointestinal transit was measured in control mice or 3 h after treatment with croton oil (0.01 ml mouse −1 ). At this time, 0.1 ml of a black marker (10% charcoal suspension in 5% gum arabic) was administered orally to assess upper gastrointestinal transit as previously described (Pol et al ., 1996; Izzo et al ., 1999a). After 20 min the mice were killed by asphyxiation with CO 2 and the gastrointestinal tract removed.…”

Section: Methodsmentioning

confidence: 99%

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Central and peripheral cannabinoid modulation of gastrointestinal transit in physiological states or during the diarrhoea induced by croton oil

Izzo

Pinto

Borrelli

et al. 2000

British J Pharmacology

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, i.p.) but not by SR144528 (52 nmol mouse 71 , i.p.) both in control and croton-oil treated mice. 5 Ganglionic blockade with hexamethonium (69 nmol mouse 71 , i.p.) did not modify the inhibitory eect of i.p.-injected cannabinoid agonists either in control or in croton-oil treated mice. 6 The lower ED 50 values of cannabinoid drugs after i.c.v. administration suggest a central (CB 1 ) site of action. However, a peripheral site of action is suggested by the lack of eect of hexamethonium. In addition, croton oil-induced diarrhoea enhances the eect of cannabinoid agonists by a peripheral mechanism.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Central and peripheral cannabinoid modulation of gastrointestinal transit in physiological states or during the diarrhoea induced by croton oil

Izzo

Pinto

Borrelli

et al. 2000

British J Pharmacology

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“…Acute inflammation was induced by the intragastric administration of 0.05 ml of croton oil (CO) according to the method described previously (Pol et al , 1994; 1996b). Two other groups of animals receiving the same volume of saline (SS) or castor oil (CA) served as controls (Pol et al , 1996c). All groups of animals were weighed and placed into separate cages.…”

Section: Methodsmentioning

confidence: 99%

Reversal of tolerance to the antitransit effects of morphine during acute intestinal inflammation in mice

Pol

Puig

1997

British J Pharmacology

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1 The aim of investigation was to establish and compare the reversibility of tolerance to the antitransit e ects of morphine by three di erent procedures: (a) acute in¯ammation of the gut, (b) lorglumide a cholecystokinin A (CCK A ) receptor antagonist, or (c) MK-801, an N-methyl-D-aspartate (NMDA) receptor ion channel blocker. The type of interaction between morphine and lorglumide or MK-801 on the inhibition of gastrointestinal transit (GIT) in naive animals was also evaluated. 2 Male Swiss CD-1 mice were implanted with 75 mg of morphine base or placebo pellets. Gastrointestinal transit was assessed with a charcoal meal and results expressed as % inhibition of GIT. In¯ammation was induced by the intragastric (p.o.) administration of croton oil (CO), while controls received castor oil (CA) or saline (SS). Morphine was administered by subcutaneous (s.c.) or intracerebroventricular (i.c.v.) injection, to naive and tolerant animals treated with CO, CA or SS. Doseresponse curves for s.c. morphine were also perforrmed in naive and tolerant mice receiving 5.2 or 7.4 nmol (s.c.) lorglumide or MK-801, respectively. 3 The ED 50 values for inhibition of GIT by s.c. morphine were: 45.9+2.7 and 250.1+3.1 nmol in naive and tolerant animals, respectively, demonstrating a ®ve fold decrease in the potency of morphine. In naive animals, in¯ammation (CO) decreased the ED 50 of morphine three times (14.4+2.2 nmol). However, no tolerance to s.c. morphine (ED 50 16.4+2.6 nmol) was manifested during intestinal in¯ammation. After i.c.v. administration, a similar degree of tolerance to morphine was observed (4.8 fold decrease in potency). Intestinal in¯ammation had no e ect on the ED 50 values of i.c.v. morphine in naive and tolerant animals, showing that reversal of tolerance is related to local mechanism/s. Mean values for intestinal pH were 6.9+0.04 and 6.2+0.04 in SS and CO treated mice, respectively. In addition, morphine was 74 times more potent by the i.c.v. than by the s.c. route (naive-SS). 4 Morphine and lorglumide interacted synergistically in naive animals; in addition, the administration of lorglumide reversed tolerance to s.c. morphine. No interaction (additivity) was observed in naive animals when morphine and MK-801 were administered in combination. However, the drug completely reversed tolerance to the antitransit e ects of morphine. 5 The present investigation shows that acute in¯ammation of the gut reverses tolerance to the antitransit e ects of s.c. morphine by a peripheral mechanism. Qualitatively similar results were obtained after the administration of lorglumide or MK-801. Our results suggest that a local decrease in pH could play an important role during in¯ammation, while antagonism of endogenous compensatory systems would explain the reversal of tolerance induced by lorglumide or MK-801.

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“…In different animal models, peripheral inflammation induces a 'sensitization' of opioid and · 2 -adrenergic receptors, enhancing the effects of exogenously administered agonists [5][6][7][8]. In the present investigation our working hypothesis was that during inflammation, encapsulated morphine would preserve the enhanced antinociceptive effects manifested by the free form, while showing a longer duration of action; thus, effective and long-lasting analgesia should be obtained with lower doses of MS-LP than MS-F.…”

Section: Introductionmentioning

confidence: 99%

Antinociceptive/Anti-Edema Effects of Liposomal Morphine during Acute Inflammation of the Rat Paw

et al. 2000

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We evaluated the anti-edema/antinociceptive effects of subcutaneous free and liposomal morphine in rats with carrageenan-induced inflammation of the paw. We assessed antinociception by the paw pressure test and edema by plethysmography. Unilamellar liposomes (150–200 nm) with 0.3% morphine hydrochloride were used; encapsulation signifcantly reduced the rate for release of morphine in vitro. During inflammation, the antinociceptive potency of free, but not liposomal morphine increased 2.5 times; moreover, duration of the effects was prolonged by encapsulation (p < 0.001). The anti-edema effects of liposomal morphine were more pronounced (p < 0.001) and of longer duration (p < 0.05). All the effects were reversed by naloxone. The results show that morphine encapsulation enhances the anti-edema effects and prolongs antinociception.

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The inhibitory effects of α₂‐adrenoceptor agonists on gastrointestinal transit during croton oil‐induced intestinal inflammation

Abstract: 1 The peripheral effects of a2-adrenoceptor agonists were investigated in a model of intestinal inflammation induced by intragastric administration of croton oil (CO). Our

Cited by 15 publications

References 28 publications

Central and peripheral cannabinoid modulation of gastrointestinal transit in physiological states or during the diarrhoea induced by croton oil

Central and peripheral cannabinoid modulation of gastrointestinal transit in physiological states or during the diarrhoea induced by croton oil

Reversal of tolerance to the antitransit effects of morphine during acute intestinal inflammation in mice

Antinociceptive/Anti-Edema Effects of Liposomal Morphine during Acute Inflammation of the Rat Paw

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The inhibitory effects of α2‐adrenoceptor agonists on gastrointestinal transit during croton oil‐induced intestinal inflammation

Abstract: 1 The peripheral effects of a2-adrenoceptor agonists were investigated in a model of intestinal inflammation induced by intragastric administration of croton oil (CO). Our

Cited by 15 publications

References 28 publications

Central and peripheral cannabinoid modulation of gastrointestinal transit in physiological states or during the diarrhoea induced by croton oil

Central and peripheral cannabinoid modulation of gastrointestinal transit in physiological states or during the diarrhoea induced by croton oil

Reversal of tolerance to the antitransit effects of morphine during acute intestinal inflammation in mice

Antinociceptive/Anti-Edema Effects of Liposomal Morphine during Acute Inflammation of the Rat Paw

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The inhibitory effects of α₂‐adrenoceptor agonists on gastrointestinal transit during croton oil‐induced intestinal inflammation