Propionate-induced epithelial K+ and Cl-/HCO3- secretion and free fatty acid receptor 2 (FFA2, GPR43) expression in the guinea pig distal colon

Propionate, a fermented product in the lumen of the large intestine, is a short-chain fatty acid (SCFA) known to have a variety of localized physiological and pathophysiological functions (e. g., luminal fluid secretion and anti-inflammatory response). In the present study, we investigated propionate-induced transepithelial ion transport and the expression of SCFA receptor, free fatty acid receptor 2 (FFA2, otherwise known as GPR43) in the guinea pig distal colon utilizing the Ussing chamber technique and immunohistochemistry. The addition of propionate to the luminal bathing solution concentration-dependently induced transient K+ and Cl- and/or bicarbonate secretion within approximately 30 s and long-lasting Cl- secretion for approximately 60 min was first identified in the present study. The transient anion secretion was tetrodotoxin (TTX)-sensitive and mediated through the cholinergic (both nicotinic and muscarinic) neural pathway, but the transient K+ and long-lasting Cl- secretion were due to TTX-insensitive mechanism. Immunohistochemistry studies showed that some chromogranin A-immunoreactive enteroendocrine cells were also immunoreactive for FFA2 but not colocalized with 5-hydroxytryptamine. In conclusion, the propionate-induced secretion consisted of the neural and non-neural three-phase secretory manner possibly mediated by the stimulation of FFA2 expressed by enteroendocrine cells.