| First Author | Rahman MM | Year | 2021 |
| Journal | Int J Mol Sci | Volume | 22 |
| Issue | 8 | PubMed ID | 33920650 |
| Mgi Jnum | J:312226 | Mgi Id | MGI:6753469 |
| Doi | 10.3390/ijms22084171 | Citation | Rahman MM, et al. (2021) Unique Regulation of Intestinal Villus Epithelial Cl(-)/HCO3(-) Exchange by Cyclooxygenase Pathway Metabolites of Arachidonic Acid in a Mouse Model of Spontaneous Ileitis. Int J Mol Sci 22(8) |
| abstractText | Electrolytes (NaCl) and fluid malabsorption cause diarrhea in inflammatory bowel disease (IBD). Coupled NaCl absorption, mediated by Na(+)/H(+) and Cl(-)/HCO3(-) exchanges on the intestinal villus cells brush border membrane (BBM), is inhibited in IBD. Arachidonic acid metabolites (AAMs) formed via cyclooxygenase (COX) or lipoxygenase (LOX) pathways are elevated in IBD. However, their effects on NaCl absorption are not known. We treated SAMP1/YitFc (SAMP1) mice, a model of spontaneous ileitis resembling human IBD, with Arachidonyl Trifluoro Methylketone (ATMK, AAM inhibitor), or with piroxicam or MK-886, to inhibit COX or LOX pathways, respectively. Cl(-)/HCO3(-) exchange, measured as DIDS-sensitive (36)Cl uptake, was significantly inhibited in villus cells and BBM vesicles of SAMP1 mice compared to AKR/J controls, an effect reversed by ATMK. Piroxicam, but not MK-886, also reversed the inhibition. Kinetic studies showed that inhibition was secondary to altered Km with no effects on Vmax. Whole cell or BBM protein levels of Down-Regulated in Adenoma (SLC26A3) and putative anion transporter-1 (SLC26A6), the two key BBM Cl(-)/HCO3(-) exchangers, were unaltered. Thus, inhibition of villus cell Cl(-)/HCO3(-) exchange by COX pathway AAMs, such as prostaglandins, via reducing the affinity of the exchanger for Cl(-), and thereby causing NaCl malabsorption, could significantly contribute to IBD-associated diarrhea. |
