Type

Journal Article

Authors

A W Baird
D C Winter
E Walsh
H M Mohan
D Collins
M Medani

Subjects

Pharmacology

Topics
prostaglandin d2 hydantoins calcium chlorides drug effects cells cultured platelet aggregation inhibitors humans pharmacology colon antagonists inhibitors ion transport receptors prostaglandin metabolism bw a868c cyclic amp prostanoid d receptor 1 human

Prostaglandin D2 regulates human colonic ion transport via the DP1 receptor. (2014)

Abstract Prostaglandin D2 is released by mast cells and is important in allergies. Its role in gastrointestinal function is not clearly defined. This study aimed to determine the effect of exogenous PGD2 on ion transport in ex vivo normal human colonic mucosa. Mucosal sheets were mounted in Ussing chambers and voltage clamped to zero electric potential. Ion transport was quantified as changes in short-circuit current. In separate experiments epithelial monolayers or colonic crypts, isolated by calcium chelation, were treated with PGD2 and cAMP levels determined by ELISA or calcium levels were determined by fluorimetry. PGD2 caused a sustained, concentration-dependent rise in short-circuit current by increasing chloride secretion (EC50=376nM). This effect of PGD2 is mediated by the DP1 receptor, as the selective DP1 receptor antagonist BW A686C inhibited PGD2-induced but not PGE2-induced rise in short-circuit current. PGD2 also increased intracellular cAMP in isolated colonic crypts with no measurable influence on cytosolic calcium. PGD2 induces chloride secretion in isolated human colonic mucosa in a concentration-dependent manner with concomitant elevation of cytoplasmic cAMP in epithelial cells. The involvement of DP2 receptor subtypes has not previously been considered in regulation of ion transport in human intestine. Since inflammatory stimuli may induce production of eicosanoids, selective regulation of these pathways may be pivotal in determining therapeutic strategies and in understanding disease.
Collections Ireland -> University College Dublin -> PubMed

Full list of authors on original publication

A W Baird, D C Winter, E Walsh, H M Mohan, D Collins, M Medani

Experts in our system

1
Alan W. Baird
University College Dublin
Total Publications: 70
 
2
Desmond C. Winter
University College Dublin
Total Publications: 53
 
3
Edwin G. Walsh
University College Dublin
Total Publications: 7
 
4
Helen M Mohan
University College Dublin
 
5
Denis M Collins
Dublin City University
Total Publications: 26