The relationship between CFTR expression and cAMP-stimulated bicarbonate secretion diverges for the duodenum and ileum of pig

Rebecca Mujica; Ian Thornell

doi:10.1152/physiol.2023.38.s1.5733469

The luminal pH of the small intestine influences the digestion and absorption of nutrients. HCO3– secretion from Brunner’s glands and the ampulla of Vater initially alkalinize the acidic chyme upon entering the small intestine, and less-frequent Brunner’s glands and the surface epithelia of the small intestine further alkalinize chyme as it moves away from the ampulla of Vater. People with cystic fibrosis alkalinize chyme more slowly than their peers, suggesting that the anion channel CFTR (cystic fibrosis transmembrane conductance regulator) participates in the alkalinization. To further understand the relationship between CFTR expression and HCO3– secretion across duodenal and ileal epithelia, we studied newborn pigs with disrupted CFTR alleles ( CFTR–/–) and their littermates ( CFTR+/– and CFTR+/+). We hypothesized that CFTR–/– pigs would lack HCO3– secretion and that CFTR+/– pigs would have decreased HCO3– secretion because of reduced CFTR expression. To measure the electrogenic HCO3– secretion rate, we recorded short-circuit current ( Isc) across resected intestinal tissue bathed in solutions containing gluconate and HCO3–. Forskolin/IBMX-stimulated Isc across the duodenum of CFTR+/– pigs was half the rate observed for CFTR+/+ pigs, and forskolin/IBMX-stimulated Isc was absent across CFTR–/– duodenum. However, Isc across the ileum was similar between CFTR+/+ and CFTR+/– pigs and absent across CFTR–/– ileum. CFTR–/– pigs expressed CFTR mRNA transcripts at nominal levels for both intestinal segments, whereas CFTR+/– pigs expressed half the CFTR mRNA transcripts of CFTR+/+ littermates for each intestinal segment. These data are consistent with CFTR involvement in neutralizing luminal contents in the duodenum and ileum. Furthermore, these data suggest that the relationship between CFTR expression and the electrogenic HCO3– secretion rate diverges for these two intestinal segments. Electrogenic HCO3– secretion in the duodenum directly relates to CFTR expression, whereas electrogenic HCO3– secretion across the ileum appears to saturate at a CFTR expression level between CFTR–/– and CFTR+/– pigs. Cystic Fibrosis Foundation Research Development Program This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

The relationship between CFTR expression and cAMP-stimulated bicarbonate secretion diverges for the duodenum and ileum of pig

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