Cyclic Guanosine Monophosphate Effects on Nutrient and Electrolyte Transport in Rabbit Ileum

Abstract

In cyclic adenosine monophosphate-related diarrheas the sodium-coupled absorptive processes for glucose and amino acids are intact, thus allowing oral use of nutrient-electrolyte solutions as a therapeutic tool. Not all bacterial enterotoxins, however, act by increasing cyclic adenosine monophosphate: it is now known that some heat-stable enterotoxins act through cyclic guanosine monophosphate. Although its effects on ion transport have been found similar to those of cyclic adenosine monophosphate, nothing is known of its possible role on intestinal nutrient transport. We have therefore investigated the effects of the cyclic nucleotide analogue 8-bromo-cyclic guanosine monophosphate (0.2 mM) on the influx (from the luminal solution into the epithelium) and on the transepithelial transport of several nutrients and of sodium in the ileal mucosa of rabbits in vitro. 8-Bromo-cyclic guanosine monophosphate completely blocked sodium-chloride coupled influx, while it did not affect the uptake of glucose, glutamic acid, lysine, phenylalanine, glycylphenylalanine, and glycylsarcosine. Also Escherichia coli heat-stable enterotoxin did not affect glucose influx measured at various. substrate concentrations. Five millimolar glucose raised sodium uptake by an identical value both in the presence and in the absence of the cyclic nucleotide analog; also, these increments were in good agreement with the uptake of glucose at 5 mM both in the absence and in the presence of heat-stable enterotoxin, thus suggesting that the sodium-glucose coupled influx is intact. We have also investigated the effects of 8-bromo-cyclic guanosine monophosphate on transepithelial transport of glucose, phenylalanine, and sodium across stripped, short-circuited ileal mucosa. Although the cyclic nucleotide analogue markedly shifted net sodium transport toward secretion, it did not alter the net absorption of either glucose or phenylalanine. We conclude that cyclic guanosine monophosphate, like cyclic adenosine monophosphate: (a) inhibits sodium chloride coupled influx and induces secretory changes on net sodium transport; (b) has no inhibitory effect on the 1:1 obligatory coupled influx of glucose and sodium across the brush border; and (c) does not affect transport of glucose, amino acids, and dipeptides. These data support the oral use of nutrient-electrolyte solutions in the treatment of heat-stable enterotoxin-induced diarrheas.