Blockade of adenosine A2B receptors ameliorates murine colitis

Background and purpose: The adenosine 2B (A2B) receptor is the predominant adenosine receptor expressed in the colon. Acting through the A2B receptor, adenosine mediates chloride secretion, as well as fibronectin and interleukin (IL)-6 synthesis and secretion in intestinal epithelial cells. A2B receptor mRNA and protein expression are increased during human and murine colitis. However, the effect of the A2B receptor in the activation of the intestinal inflammatory response is not known. In this study, we examined the effect of A2B receptor antagonism on murine colitis. Experimental approach: Dextran sodium sulphate (DSS)-treated mice and piroxicam-treated IL-10/ mice were used as animal models of colitis. The A2B receptor-selective antagonist, ATL-801, was given in the diet. Key results: Mice fed ATL-801 along with DSS showed a significantly lower extent and severity of colitis than mice treated with DSS alone, as shown by reduced clinical symptoms, histological scores, IL-6 levels and proliferation indices. The administration of ATL-801 prevented weight loss, suppressed the inflammatory infiltrate into colonic mucosa and decreased epithelial hyperplasia in piroxicam-treated IL-10/ mice. IL-6 and keratinocyte-derived chemokine (KC) concentrations in the supernatants of colonic organ cultures from colitic mice were significantly reduced by ATL-801 administration. Conclusions and implications: Taken together, these data demonstrate that the intestinal epithelial A2B receptor is an important mediator of pro-inflammatory responses in the intestine and that A2B receptor blockade may be an effectiv

Effects of experience and body size on refuge choice in the crayfish Orconectes immunis

We investigated whether refuge size or experience with a refuge affected the refuge use of male Orconectes immunis crayfish. Individuals were given choices among seven refuges for 10 consecutive days. Refuges were formed from equal length but different diameter PVC pipe and placed in an array in a random sequence. Three treatments were used. In the Novel Refuge treatment, individuals were placed in a new test arena with a new arrangement of cleaned refuges every day. In the Nonremoval treatment, individuals were left in the same arena with the same set of refuges each day. In the Removal treatment, individuals were removed from the refuges each day but placed back in the same arena with the same set of refuges after the refuges had been cleaned. We found that refuge occupation was correlated with an individual\u27s size; smaller crayfish tended to use smaller refuges than larger crayfish, even though all crayfish could fit in all of the different sized refuges. When first tested, individuals initially chose larger refuges than they would subsequently settle in, suggesting that under duress, they were not as particular about refuge characteristics. Individuals in the Nonremoval and Removal treatments were significantly more consistent in their refuge use than those in the Novel Refuge treatment, suggesting that experience with a particular refuge increased use of that refuge. Individuals from the Novel Refuge treatment that were housed for a month with a single refuge did not increase their use of that sized refuge more than those that were housed without a refuge, indicating that simply occupying a refuge of a given size did not affect refuge preference