41 research outputs found
Endocannabinoids-related compounds in gastrointestinal diseases
The endocannabinoid system (ECS) is an endogenous signalling pathway involved in the control of several gastrointestinal (GI) functions at both peripheral and central levels. In recent years, it has become apparent that the ECS is pivotal in the regulation of GI motility, secretion and sensitivity, but endocannabinoids (ECs) are also involved in the regulation of intestinal inflammation and mucosal barrier permeability, suggesting their role in the pathophysiology of both functional and organic GI disorders. Genetic studies in patients with irritable bowel syndrome (IBS) or inflammatory bowel disease have indeed shown significant associations with polymorphisms or mutation in genes encoding for cannabinoid receptor or enzyme responsible for their catabolism, respectively. Furthermore, ongoing clinical trials are testing EC agonists/antagonists in the achievement of symptomatic relief from a number of GI symptoms. Despite this evidence, there is a lack of supportive RCTs and relevant data in human beings, and hence, the possible therapeutic application of these compounds is raising ethical, political and economic concerns. More recently, the identification of several EC-like compounds able to modulate ECS function without the typical central side effects of cannabino-mimetics has paved the way for emerging peripherally acting drugs. This review summarizes the possible mechanisms linking the ECS to GI disorders and describes the most recent advances in the manipulation of the ECS in the treatment of GI diseases
T1301 Acute Colonic Ischemia in Rats Is Associated to a Local, Long-Term, Infiltration of Mast Cells Without Alterations of Colonic Sensitivity
T1451 Oral Pregabalin Inhibits Visceral Pain Responses to Colorectal Distension and Increases Colonic Compliance in Rats
T1252 The Selective 5-HT1A Antagonist, AZD7371 (Robalzotan Tartrate Monohydrate), Inhibits Pain-Related Visceromotor, But Not Autonomic Cardiovascular, Responses to Colorectal Distension in Rats
New Telemetry Device for the Measurement of Gastrointestinal Motility in Rats and Comparison With Standard Equipment
Effect of HSA-NEPv on PT and APTT in rats.
<p>Mean (± SD) PT (A) and APTT (B) in rats after twice weekly administration of HSA-NEPv at dose levels of 0 (vehicle control), 5, 50 or 143 mg/kg for 1 month (n = 5 animals/gender/group). PT and APTT were measured on Day 26 (the day after the eighth dose). *<i>P</i> <0.05; **<i>P</i> < 0.01 compared with control.</p
Effect on HSA-NEPv on PT and APTT in cynomolgus monkeys.
<p>Mean (± SD) PT (A) and APTT (B) were measured in male cynomolgus monkeys four days before dosing (Predose) and 24 h after administration (Day 2) of HSA-NEPv at dose levels of 0 (vehicle control), 5, 50 or 143 mg/kg (n = 3). **<i>P</i> < 0.01 compared with control.</p
Cleavage sites of NEP wild type and NEPv in fibrinogen α- and β-chains and effect on FpA release by thrombin.
<p>Cleavage patterns for NEP wild type and NEPv on human, cynomolgus monkey and rat fibrinogen α- and β-chains were determined by N-terminal sequencing (A). Cleavage sites for NEP are indicated by arrows while those for thrombin are labelled *. Cleavage of full-length and truncated human or rat FpA by thrombin (B and C). Rates of cleavage were determined for full-length (●) or NEP-truncated (□) human (B) or rat (C) FpA by human or rat thrombin, respectively. The Michaelis-Menten equation was used to fit the data. Error bars represent SD (n = 3) and data are representative of two replicate experiments.</p