Effect of short-chain fatty acids on cell volume and intracellular pH in rat distal colon.
Superfusion of isolated crypts from the rat colon with sodium-butyrate-containing solutions induced an increase in the crypt diameter indicating a swelling of the crypt cells. The response to butyrate (50 mmol l-1) was not uniform along the crypt axis, the most pronounced swelling being observed in the upper third of the crypt. The butyrate effect was concentration-dependent and was completely suppressed by amiloride, suggesting that it is caused by activation of the Na+/H+ exchanger. Acetate, propionate and isobutyrate had a similar action. In HEPES-buffered solution the butyrate-induced change in cell volume was monophasic, i. e. only a swelling took place, whereas in HCO3- buffer it was biphasic, i. e. swelling was followed by a regulatory volume decrease. This decrease was suppressed by K+ and Cl- channel blockers as well as inhibitors of leukotriene synthesis. Measurements of intracellular pH with the fluorescent dye 2',7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein (BCECF) revealed that butyrate induced an acidification of the cell, which was stronger in HEPES than in HCO3- buffer. Estimation of Na+/H+ exchange activity, tested as recovery of intracellular pH from an acid load via an NH4Cl prepulse, revealed a much lower Na+/H+ exchange activity in the fundus region compared to the upper third of the crypt. The smaller volume response evoked by butyrate in the fundus region probably reflects the smaller Na+/H+ activity compared to the more differentiated cells near the opening of the crypt. It is concluded that cell swelling caused by short-chain fatty acids is a physiological stimulus for volume regulation. This response is restricted to the more differentiated cells.
Diener
M
M
Institut für Veterinär-Physiologie, Universität Zürich, Switzerland.
Helmle-Kolb
C
C
Murer
H
H
Scharrer
E
E
D000818:Animals; D016718:Arachidonic Acid / Q000037:antagonists & inhibitors / Q000378:metabolism; D002087:Butyrates / Q000494:pharmacology; D020148:Butyric Acid; D018118:Chloride Channels / Q000378:metabolism; D003106:Colon / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D005227:Fatty Acids / Q000494:pharmacology*; D005260:Female; D005452:Fluoresceins; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D015221:Potassium Channels / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D017923:Sodium-Hydrogen Exchangers / Q000378:metabolism
D002087:Butyrates; D018118:Chloride Channels; D005227:Fatty Acids; D005452:Fluoresceins; D015221:Potassium Channels; D017923:Sodium-Hydrogen Exchangers; D020148:Butyric Acid; D016718:Arachidonic Acid; C043829:2',7'-bis(carboxyethyl)-5(6)-carboxyfluorescein