Deciphering ion transporters, kinases and PDZ-adaptor molecules that mediate guanylate cyclase C agonist-dependent intestinal fluid loss in vivo

Inhibition of Na+/H+ exchanger isoform 3 improves gut fluidity and alkalinity in cystic fibrosis transmembrane conductance regulator‐deficient and F508del mutant mice

“…However, we had not observed this difference in previous experiments in which buffered solutions had been perfused (Liu et al, 2020). During luminal perfusion of the jejunum with unbuffered solution the pH decreased in WT mice and significantly more so in ko/mut mice (Table 2).…”

“…F508del mut/mut jejunum, but not in the colon 10 -7 M luminally applied linaclotide had elicited a robust Isc response in murine jejunal (Liu, Tan et al, 2020) and rat proximal colonic (Ahsan, Tchernychev et al, 2017) isolated mucosa.…”

“…The basal fluid absorptive rates and HCO 3 − output rates were not significantly different between F508del mut/mut and cftr −/− intestine. Linaclotide, 10 −7 M, applied luminally had been shown to elicit a robust short circuit current response in murine jejunal (Liu et al, 2020) and rat proximal colonic (Ahsan et al, 2017) isolated mucosa. In this study, it also stimulated a short circuit current response in isolated jejunal, proximal and distal colonic mucosa that was absent in cftr −/− , minimal in F508del mut/mut and robust in WT jejunal, proximal colonic and lower in mid-distal colonic mucosa (Figure S3).…”

Strategies for cystic fibrosis transmembrane conductance regulator inhibition: from molecular mechanisms to treatment for secretory diarrhoeas

“…As predicted, mice deficient in GC‐C are STa‐ but not CT‐resistant [65]. In contrast, PKG2 ablation in mice reduced the effect of STa on jejunal I sc by 80%, but diminished jejunal fluid loss in vivo by only 50%, most likely due to a CT‐like action of STa on 5‐HT release by EC cells, followed by an ENS‐mediated release of VIP that signals through cAMP, not cGMP [66–68].…”

The role of NHE3 (Slc9a3) in oxalate and sodium transport by mouse intestine and regulation by cAMP

“…The cohorts used in this study were approximately one third the age of their WT counterparts due to poor survivability of NHE3 KO mice, despite providing Pedialyte®. Poor survivability is a limitation of working with this KO model as noted previously (Liu et al, 2020) and the decision was made to conduct the experiments without age-matched cohorts due to uncertainty over the ability and timescale to generate sufficient numbers again and because we have not previously seen any large correlations between age and intestinal oxalate fluxes, I sc or G T when examining results from WT mice between 62 and 318 days old (unpublished data). Despite the age difference, body mass was not different between WT and NHE3 KO mice (Table 1).…”