Propionate-initiated changes in intracellular pH in rabbit colonocytes.
OBJECTIVE
Because regulation of intracellular pH (pHi) is critical to basic cell functions, most cells have evolved mechanisms to closely regulate intracellular acid-base balance. Short-chain fatty acids (SCFAs), the predominant luminal anion in the colon, acidify the cell interior in several cell systems, but their effect on their "natural target," the colonocytes, has not been examined thoroughly.


METHODS
We monitored the pHi response to a model SCFA, propionate, in isolated cells and epithelial sheets from rabbit proximal colon loaded with the pH-sensitive dye 2',7'-bis-(2-carboxyethyl)-5-(and -6)carboxyfluorescein.


RESULTS
SCFAs induced a characteristic pHi response curve in colonocytes: an immediate acidification and a recovery phase returning to baseline in 100-200 seconds. Acidification was altered by increasing concentrations of SCFAs, by increasing SCFA chain length, extracellular osmolarity, and intracellular pH, and finally, Na+ removal. The recovery phase was slowed by amiloride and 4-alpha-OH cinnamate, an inhibitor of proton-monocarboxylate cotransport.


CONCLUSIONS
Physiological concentrations of SCFAs have profound effects on intracellular pH. Simple diffusion of the SCFA may not explain the complexities of propionate-induced protonated acidification; the pH recovery phase may involve multiple processes including Na(+)-H+ exchange and H(+)-SCFA cotransport. Luminal constituents such as SCFAs may have significant effects on the intracellular pH and function of colonocytes.
Department of Internal Medicine, University of Texas Medical School at Houston.
R
R
DeSoignie
J H
JH
Sellin
D000136:Acid-Base Equilibrium / Q000187:drug effects; D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D002264:Carboxylic Acids / Q000378:metabolism; D003106:Colon / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D003373:Coumaric Acids / Q000494:pharmacology; D004058:Diffusion; D005232:Fatty Acids, Volatile / Q000502:physiology; D006859:Hydrogen / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D017136:Ion Transport / Q000187:drug effects; D008297:Male; D009994:Osmolar Concentration; D011422:Propionates / Q000493:pharmacokinetics / Q000494:pharmacology*; D011817:Rabbits; D012964:Sodium / Q000378:metabolism
D002264:Carboxylic Acids; D003373:Coumaric Acids; D005232:Fatty Acids, Volatile; D011422:Propionates; D000584:Amiloride; D006859:Hydrogen; D012964:Sodium