Gastrointestinal Motility In Mice Research Articles

English

The aqueous extract of Boswelli dalzielii Hutch (family: Burseraceae) was investigated for therapeutic properties using aspirin-induced ulceration in rats, gastrointestinal motility in mice and castor oil-induced diarrhoea in rats. The median lethal dose (LD 50 ) of the extract was carried out via the oral route in mice. Antimicrobial and preliminary phytochemical screening of the extract was also investigated. The extract did not show toxicity signs or death at doses O.O5) protection against castor oil-induced diarrhoea in rats. No antimicrobial effects were shown by the extract (200 mg/kg) against any of the tested organisms. Tannins were detected in the aqueous extract. The above results show that B. dalzielii stem bark probably contains some active ingredients that could be developed for such gastrointestinal problems as have been claimed by traditional medical practitioners. Key words: . African Journal of Biotechnology Vol.3(5) 2004: 284-288

A Diterpenoid fromSalvia cinnabarinaInhibits Mouse Intestinal Motilityin vivo

This study was aimed to investigate the effect of 3,4 secoisopimara-4(18),7,15-trien-3-oic acid (compound 1) isolated from the aerial parts of Salvia cinnabarina, on upper gastrointestinal transit in mice in vivo. Compound 1 (10 - 100 mg/kg, i. p.) dose-dependently delayed gastrointestinal motility. Pretreatment ( i. p.) of mice with hexamethonium (10 mg/kg), naloxone (2 mg/kg), N(G)-nitro- L-arginine-methyl ester ( L-NAME) (25 mg/kg) or yohimbine (1 mg/kg) did not modify the inhibitory effect of compound 1 (50 mg/kg). However, the L-type Ca (2+) channel verapamil (5 mg/kg, i. p.) significantly reduced the antimotility effect of compound 1 (50 mg/kg). These results suggest that compound 1 inhibits gastrointestinal motility in mice. The effect could involve, at least in part, L-type Ca (2+) channels.

Smooth muscle contraction induced by Indigofera dendroides leaf extracts may involve calcium mobilization via potential sensitive channels.

The contractile effects of the aqueous extract of the leaves of Indigofera dendroides (ID) were studied on the gastrointestinal motility in mice and isolated smooth muscle preparations obtained from rats and guinea pigs. The contractile effects of 10(-6) M acetylcholine, 80 mM KCl and 1.6 mg/ml ID were measured on the rat ileal smooth muscle exposed to calcium-free buffer or physiological solution, to determine the calcium pools mobilized by extract for activation of contraction. Acute toxicity test (LD(50)) was also carried out in mice. The result showed that ID (0.05-3.2 mg/ml) produced a concentration-dependent contraction of the guinea pig and rat ileum. These responses were not blocked by mepyramine (2.49 x 10(-9) M), verapamil (8.14 x 10(-9) M), or pirenzepine (4.7 x 10(-7) M), but were blocked completely by atropine (2.92 x 10(-9) M). A significant increase in propulsion of gastrointestinal motility was observed. Acetylcholine, KCl and ID produced contractions in Ca(2+) free media. The phasic components of the contractile responses to Ach as well as the tonic component of K(+) and ID-induced contractions were relatively resistant to short periods of calcium-free exposure. Ach, K(+) and ID still caused contractions in the presence of verapamil. The data revealed that ID-induced contractions were not mediated by histaminergic receptors, calcium channels, M1 muscarinic receptors. It also suggests that Ach mobilize Ca from some tightly bound or intracellular pool, whereas high K(+) and ID may mobilize Ca from some superficial or loosely-bound pool.

Inhibitory effect of palmitoylethanolamide on gastrointestinal motility in mice.

1. We have studied the effect of palmitoylethanolamide (PEA, 2.5 - 30 mg kg(-1), i.p.) on upper gastrointestinal transit in control mice and in mice with chronic intestinal inflammation induced by croton oil. 2. PEA significantly and dose-dependently decreased intestinal transit. The inhibitory effect of PEA (10 mg kg(-1)) was not modified by the cannabinoid CB(1) receptor antagonist SR141716A (0.3 mg kg(-1), i.p.), the cannabinoid CB(2) receptor antagonist SR144528 (1 mg kg(-1), i.p.), N(G)-nitro-L-arginine methyl ester (L-NAME, 25 mg kg(-1), i.p.), yohimbine (1 mg kg(-1), i.p.), naloxone (2 mg kg(-1), i.p.) or hexamethonium (1 mg kg(-1), i.p.). 3. PEA levels were significantly decreased in the small intestine of croton oil-treated mice. In these animals, PEA also inhibited motility and this effect was not counteracted by SR141716A (0.3 mg kg(-1)), or SR144528 (1 mg kg(-1)). 4. Pre-treatment of mice with the amidase inhibitor phenylmethyl sulphonil fluoride (PMSF, 30 mg kg(-1), i.p.) did not modify the inhibitory effect of PEA, either in control or in mice with inflammation. 5. It is concluded that PEA inhibits intestinal motility with a peripheral mechanism independent from cannabinoid receptor activation. The decreased levels of PEA in croton oil-treated might contribute, at least in part, to the exaggerated transit observed during chronic intestinal inflammation.

Cannabinoid CB1-receptor mediated regulation of gastrointestinal motility in mice in a model of intestinal inflammation.

1. We have studied the effect of cannabinoid agonists (CP 55,940 and cannabinol) on intestinal motility in a model of intestinal inflammation (induced by oral croton oil in mice) and measured cannabinoid receptor expression, endocannabinoids (anandamide and 2-arachidonylglycerol) and anandamide amidohydrolase activity both in physiological and pathophysiological states. 2. CP 55,940 (0.03 - 10 nmol mouse(-1)) and cannabinol (10 - 3000 nmol mouse(-1)) were more active in delaying intestinal motility in croton oil-treated mice than in control mice. These inhibitory effects were counteracted by the selective cannabinoid CB(1) receptor antagonist SR141716A (16 nmol mouse(-1)). SR141716A (1 - 300 nmol mouse(-1)), administered alone, increased intestinal motility to the same extent in both control and croton oil-treated mice. 3. Croton oil-induced intestinal inflammation was associated with an increased expression of CB(1) receptor, an unprecedented example of up-regulation of cannabinoid receptors during inflammation. 4. High levels of anandamide and 2-arachidonylglycerol were detected in the small intestine, although no differences were observed between control and croton oil-treated mice; by contrast anandamide amidohydrolase activity increased 2 fold in the inflamed small intestine. 5. It is concluded that inflammation of the gut increases the potency of cannabinoid agonists possibly by 'up-regulating' CB(1) receptor expression; in addition, endocannabinoids, whose turnover is increased in inflamed gut, might tonically inhibit intestinal motility.

A simple method to investigate the inhibitory effects of drugs on gastric emptying in the mouse in vivo

Introduction: The aim was to develop a simple method to study modification of gastric motility in the mouse in vivo. Methods: Mice were fed a hydrated diet in which the fluid content of standard laboratory chow was increased by adding water. Gastric emptying was assessed at specified times following a 1-h treatment period with orally administered pharmacological agents. Results: We demonstrated consistent and progressive gastric emptying over a 4-h period, stomach content being decreased from 7.52±0.90 at time zero to 2.80±0.25 mg/g body weight after 4 h. Results demonstrated typical effects of inhibitory agents (atropine and morphine) and showed inhibitory effects of three potassium channel opening agents, pinacidil, cromakalim, and SDZ PCO400: the residue remaining in the stomach was increased by 3.66±0.84, 6.56±1.35, and 5.68±1.33 mg/g body weight respectively 1 h after treatment with 10 mg/kg of these agents, compared to vehicle controls. Discussion: The inhibitory activity observed correlated well with previous studies on the effects of potassium channel opening agents on mouse gastrointestinal motility in vivo and in vitro. The present model may thus be of value in the pharmacological investigation of gastrointestinal motility owing to cost and convenience advantages, together with the possibility of its application to studies using transgenic animals.

Effect of vanilloid drugs on gastrointestinal transit in mice.

1. We have studied the effect of capsaicin, piperine and anandamide, drugs which activate vanilloid receptors and capsazepine, a vanilloid receptor antagonist, on upper gastrointestinal motility in mice. 2. Piperine (0.5 - 20 mg kg(-1) i.p.) and anandamide (0.5 - 20 mg kg(-1) i.p.), dose-dependently delayed gastrointestinal motility, while capsaicin (up to 3 mg kg(-1) i.p.) was without effect. Capsazepine (15 mg kg(-1) i.p.) neither per se affected gastrointestinal motility nor did it counteract the inhibitory effect of both piperine (10 mg kg(-1)) and anandamide (10 mg kg(-1)). 3. A per se non effective dose of SR141716A (0.3 mg kg(-1) i.p.), a cannabinoid CB(1) receptor antagonist, counteracted the inhibitory effect of anandamide (10 mg kg(-1)) but not of piperine (10 mg kg(-1)). By contrast, the inhibitory effect of piperine (10 mg kg(-1)) but not of anandamide (10 mg kg(-1)) was strongly attenuated in capsaicin (75 mg kg(-1) in total, s.c.)-treated mice. 4. Pretreatment of mice with N(G)-nitro-L-arginine methyl ester (25 mg kg(-1) i.p.), yohimbine (1 mg kg(-1), i.p.), naloxone (2 mg kg(-1) i.p.), or hexamethonium (1 mg kg(-1) i.p.) did not modify the inhibitory effect of both piperine (10 mg kg(-1)) and anandamide (10 mg kg(-1)). 5. The present study indicates that the vanilloid ligands anandamide and piperine, but not capsaicin, can reduce upper gastrointestinal motility. The effect of piperine involves capsaicin-sensitive neurones, but not vanilloid receptors, while the effect of anandamide involves cannabinoid CB(1), but not vanilloid receptors.

Evaluation of the Antiulcer Properties of<i> Pseudocedrela kotschyi</i> Stem Bark Extract

Aqueous stem bark extract of Pseudocedrela kotschyi, Harms (Meliaceae) was investigated for antiulcer activity. The extract neither contracted nor relaxed the isolated guinea pig ileum. It however, inhibited the contraction evoked by acetylcholine and histamine in a doserelated manner. Gastrointestinal motility in mice was significantly (p

Antispasmodic activity of the fruits of Helicteres isora Linn.

Fruits of Helicteres isora Linn., commonly called Murudsheng in India, are usually prescribed in the Indian traditional systems of medicine, especially in Ayurveda, for a variety of intestinal complaints. The antispasmodic activity was checked in vitro on guinea-pig ileum against three spasmogens, acetylcholine, histamine and barium chloride. The IC(50) for each was determined. The activity was compared with standard antispasmodic agents, atropine and diphenhydramine hydrochloride. The activity was also studied in vivo by observing the gastrointestinal motility in mice using the marker technique and the ED(50) was calculated. Acute toxicity studies were conducted on mice using the method of Weil and the LD(50) was determined. The results indicated that the fruits possess very good antispasmodic activity.

Spasmolytic Activity ofCissampelous mucronataLeaf Extract

The aqueous leaf extract of Cissampelous mucronata (Menispermaceae) was studied for spasmolytic properties. The extract inhibited the responses of histamine, acetylcholine and nicotine on the guinea-pig ileum in a doserelated manner. The extract completely abolished the spontaneous pendular movement of the rabbit jejunum reversibly, and decreased gastrointestinal motility in mice. It did not modify the effect of Ca 2+ on the guinea-pig ileum. Acute toxicity tests in mice established the i.p. LD 50 value of the extract to be 1698.24±77 mg/kg.

Effects of ketamine on nociception and gastrointestinal motility in mice are unaffected by naloxone

1. 1. The present study investigates the effects of ketamine on nociception towards chemical and thermic stimuli and on gastrointestinal transit in mice. 2. 2. The reversibility of these effects by the opioid antagonist naloxone (10 mg/kg) was also assessed. 3. 3. Ketamine promoted dose-related analgesia in both the acetic acid-induced writhing and hot plate tests. 4. 4. Analgesia was not influenced by pretreatment with naloxone. 5. 5. Contrasting the constipation induced by opioids, ketamine enhanced gastrointestinal transit in a dose-dependent manner and this was not modified by naloxone. 6. 6. These results suggest that although ketamine can elicit analgesia, it does not activate opioid mechanisms in subanesthetic doses.

M&B 28,767: A potent anti-secretory and anti-ulcer PG analogue a comparative study with 16, 16′ dimethyl PGE 2 methylester

M&B 28,767 [(±)11-deoxy-16-phenoxy-ω-tetranor PGE 1] and 16, 16′-dimethyl PGE 2 methylester (DMPG) were compared for their effects on gastric acid secretion (GAS) and gastric ulceration (GU), employing various laboratory models. In anaesthetised rats, GAS was stimulated by a continuous i.v. infusion of pentagastrin (30 >g/kg/h), and PG analogues were perfused through the stomach for 1 h. M&B 28,767 (3–15 >g/kg/h) and DMPG (3–60 >g/kg/h) reduced GAS in a dose-related manner, the ED50 values being 4 and 15 >g/kg/h respectively. In conscious rats possessing indwelling gastric cannulae, oral doses of M&B 28,767 (0.025–0.1 >g/kg) and DMPG (0.50–1.0 >g/kg) caused a prolonged inhibition of pentagastrin-stimulated GAS. M&B 28,767 was 17 times more potent than DMPG; the respective ED50 values were 0.036 and 0.6 >g/kg. Indomethacin-induced ulceration in rats, was reduced by both M&B 28,767 and DMPG; the respective ED50 values being 3.0 and 0.8 >g/kg. Both compounds given orally increased gastrointestinal motility in mice; M&B 28,767 (1–3 mg/kg) and DMPG (0.1–0.3 mg/kg) caused diarrhoea, the former being about 0.1 times as potent as the latter. In another test, M&B 28,767 (0.5–5.0 mg/kg) and DMPG (10–40 >g/kg) overcame morphine-induced constipation in a dose-related manner, the respective ED50s being 0.9–1.4 mg/kg and 20–40 >g/kg. Thus, M&B 28,767 had a better profile of activity than DMPG as an antisecretory and antiulcer agent.