Effect of N-methyl-d-aspartate receptor blockade on neuronal plasticity and gastrointestinal transit delay induced by ischemia/reperfusion in rats.

Intestinal ischemia impairs gastrointestinal motility. The aims of this study were to investigate the effect of intestinal ischemia on gastrointestinal transit and on the expression of enteric transmitters in the rat, and whether the glutamate N-methyl-d-aspartate receptors influence these effects. Ischemia (1 h), induced by occluding the superior mesenteric artery, was followed by 0 or 24 h of reperfusion. Normal and sham-operated rats served as controls. Serosal blood flow was measured with laser Doppler flow meter. Gastrointestinal transit was measured as time of appearance of a marker in fecal pellets. Immunohistochemistry was used to evaluate the number of neurons immunoreactive for neuronal nitric oxide synthase (NOS) or vasoactive intestinal polypeptide and the density of substance P immunoreactive fibers in the myenteric plexus. The N-methyl-d-aspartate receptors antagonist, (+)-5-methyl-10,11-dihydro-5HT-[a,b] cyclohepten-5,10-imine (MK-801) (1 mg/kg i.v.) or the NOS inhibitor, N-nitro-l-arginine (10 mg/kg i.v.) was administered prior to ischemia. Serosal blood flow was decreased by 70% during ischemia, but it was not altered in sham-operated rats. Gastrointestinal transit was significantly prolonged in ischemic/reperfused rats compared with controls. There was a significant increase in the number of vasoactive intestinal polypeptide and neuronal nitric oxide synthase immunoreactive neurons, and a marked decrease of substance P immunoreactive fibers in ischemia followed by 24 h of reperfusion animals compared with controls. These alterations were not observed in ischemia without reperfusion. A significant delay of gastrointestinal transit and increase of vasoactive intestinal polypeptide neurons were also observed in sham-operated rats. The changes in transmitter expression and gastrointestinal transit in ischemic/reperfused rats were prevented by pre-treatment with the NOS inhibitor, N-nitro-l-arginine or the N-methyl-d-aspartate receptors antagonist, MK-801. This study suggests an involvement of the glutamatergic system and its interaction with nitric oxide in intestinal ischemia/reperfusion. Ischemia/reperfusion might induce local release of glutamate that activates N-methyl-d-aspartate receptors leading to increased production of nitric oxide and adaptive changes in enteric transmitters that might contribute to gastrointestinal dysmotility.

Antinociceptive and gastroprotective effects of inhaled and orally administered Lavandula hybrida Reverchon "Grosso" essential oil.

In this study the antinociceptive and the gastroprotective effects of orally administered or inhaled Lavandula hybrida Reverchon "Grosso" essential oil, and its principal constituents linalool and linalyl acetate were evaluated in rodents. Either when orally administered (100 mg/kg) or inhaled for 60 min lavender essential oil significantly reduced the acetic acid-writhing response in a naloxone-sensitive manner. In the hot plate test, analgesic activity observed after oil inhalation was inhibited by naloxone, atropine, mecamylamine pretreatment suggesting the involvement of opioidergic as well as cholinergic pathways. Regardless of the administration route and the experimental model used both linalool and linalyl acetate did not produce significant analgesic response. Oral or inhalatory treatment with analgesic doses of essential oil did not affect mice spontaneous locomotor activity. Concerning the gastric effects, lavender oil, linalool and linalyl acetate oral administration protected against acute ethanol-induced gastric ulcers but did not prevent indomethacin-induced lesions indicating no interference with arachidonic acid metabolic cascade. In conclusion, besides this gastroprotection, lavender oil reveals an interesting analgesic activity mainly relevant after inhalation, at doses devoid of sedative side effect, suggesting the interest for potential application of this oil in aromatherapy.

Different role of the histamine H3-receptor in vagal-, betanechol-, pentagastrin-induced gastric acid secretion in anaesthetized rats.

BACKGROUND: To date, involvement of the histamine H3-receptor in the control of gastric acid secretion in rats is not conclusively defined because of the variability of experimental results. This study was therefore aimed at investigating the role of H3-receptors in acid secretion produced by nervous or pharmacological stimulation in anaesthetized rats. METHODS: Gastric acid output was measured by flushing the rat stomach lumen with 5 ml saline and titrating the flushed perfusate. Hypersecretory responses were evoked through direct vagal stimulation (0.5 msec, 10 Hz, 50 V for 30 min every 30 min) or by stimulation with pentagastrin (20, 40, 100, 250 microg/kg/h i.v.) or betanechol (100, 250, 500 microg/kg/h i.v.). The selective H3 ligands (R)-alpha-methylhistamine and thioperamide (100 microg/kg i.v.) were tested alone or in combination on both basal and electrically/pharmacologically induced secretion. RESULTS: Vagally-induced response was significantly reduced by the agonist R-alpha-methylhistamine and this effect was antagonized by the antagonist thioperamide at a dose unable by itself to modify vagal response. Thioperamide significantly increased acid response only on pentagastrin low dose (20 microg/kg/h) and this effect was counteracted by R-alpha-methylhistamine, which was ineffective when administered alone. Betanechol-induced hypersecretion was substantially unaffected by the H3 ligands, which were also inactive on basal acid output. CONCLUSIONS: Although this functional study confirms the presence of histamine H3-receptors in the rat stomach, they appear to have minor weight in regulation of the acid secretion in this species.