Mechanisms of carbachol-induced alterations in K+ transport across the rat colon.
The effect of carbachol, an agonist of the Ca2+ pathway, on K+ transport in rat proximal and distal colon was studied by measuring unidirectional fluxes, uptake, and efflux of Rb+, a marker for K+, in mucosa-submucosa preparations. Unidirectional ion flux measurements revealed that carbachol stimulated K+ secretion in the proximal colon by a marked increase in the serosa-to-mucosa flux (J(Rb)sm) and a more moderate rise in the mucosa-to-serosa flux (J(Rb)ms). In the distal colon carbachol had no effect on J(Rb)ms but J(Rb)sm was reduced after a transient increase finally resulting in an inhibition of K+ secretion. Carbachol caused a stimulation of mucosal Rb+ uptake in the distal colon, which was diminished in the presence of inhibitors of the apical H+-K+-ATPase, vanadate and ouabain. In contrast, in the proximal colon the serosal Rb+ uptake was enhanced by carbachol, an effect, which could be prevented by bumetanide, an inhibitor of the basolateral Na+-K+-2Cl(-)-cotransporter. Efflux experiments revealed that carbachol caused a transient increase of apical and basolateral Rb+ permeability in both colonic segments. In the distal colon, stimulated K+ efflux to the serosal side was reduced by quinine, efflux to the mucosal side was blocked by tetraethylammonium. In the proximal colon, carbachol-activated apical and basolateral K+ efflux were inhibited by Ba2+. In conclusion, these data suggest that in the distal colon carbachol stimulates the H+-K+-ATPase and the basolateral K+ efflux through quinine-sensitive K+ channels, whereas in the proximal colon carbachol induces K+ secretion due to a stimulation of the basolateral Na+-K+-2Cl(-)-cotransporter and an increased efflux to the luminal side via Ba2+-sensitive apical K+ channels.
Heinke
B
B
Institut für Veterinär-Physiologie, Justus-Liebig-Universität Giessen, Germany.
Hörger
S
S
Diener
M
M
D000818:Animals; D002034:Bumetanide / Q000494:pharmacology; D002118:Calcium / Q000502:physiology; D002217:Carbachol / Q000494:pharmacology*; D003106:Colon / Q000187:drug effects* / Q000378:metabolism; D004232:Diuretics / Q000494:pharmacology; D004579:Electron Transport / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D010042:Ouabain / Q000494:pharmacology; D010277:Parasympathomimetics / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000378:metabolism; D015221:Potassium Channels / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D012413:Rubidium / Q000378:metabolism / Q000493:pharmacokinetics
D004232:Diuretics; D004791:Enzyme Inhibitors; D010277:Parasympathomimetics; D015221:Potassium Channels; D002034:Bumetanide; D010042:Ouabain; D002217:Carbachol; D012413:Rubidium; D011188:Potassium; D002118:Calcium