Background & Aims Heterologous expression studies have demonstrated that the NHERF adapter proteins can bind to CFTR and modulate its conductivity and interaction with other transporter proteins. The aim of this investigation was to elucidate the role of these adaptor proteins in regulation of murine duodenal HCO3- secretion in vivo.

Methods Basal and stimulated duodenal HCO3- secretion was examined in the NHERF1, E3KARP, PDZK1, double (NHERF1 and PDZK1) and triple (NHERF1/E3KARP/PDZK1) +/+ and -/- mice by in vivo perfusion and back-titration.

Results Basal HCO3- secretory rates were similar in E3KARP +/+ and -/- mice, but significantly reduced in mice deficient for NHERF1 (40% of wt), PDZK1 (45%), double (38%) and triple (53%). The secretory response to forskolin was significantly reduced only in the NHERF1 (47% of wt), double (36%) and triple (53%) knockout mice.

ConclusionThe absence of the adapter proteins NHERF1 as well as PDZK1 resulted in significantly reduced basal HCO3- secretion, but the duodenal HCO3- secretory response to elevated cAMP only depends on NHERF1. Therefore the major NHERF adaptor protein involved in regulation of duodenal bicarbonate secretion is NHERF1.