Journal article

Publication year: 1996

Pages: 1477-1487

Journal: British Journal of Pharmacology

Volume number: 118

Issue number: 6

ISSN: 0007-1188

eISSN: 1476-5381

DOI Link: https://doi.org/10.1111/j.1476-5381.1996.tb15563.x

Publisher: Wiley

Abstract: 
1 The effect of agonists of the cyclic AMP pathway and of 293B, a chromanole-derived K+ channel blocker, on K+ transport in the rat distal colon was studied by measuring unidirectional fluxes, uptake, and efflux of Rb+ in mucosa-submucosa preparations and by patch-clamp of crypt epithelia from isolated crypts.2 293B concentration-dependently inhibited basal and forskolin-stimulated short-circuit current. In isolated crypts 293B blocked a basal K+ conductance but had no effect on cyclic AMP-evoked depolarization induced by the opening of apical Cl- channels. When the effect of cyclic AMP on Cl- conductance was prevented by substituting Cl- with gluconate, an inhibition of total cellular K+ conductance by forskolin and a membrane-permeable cyclic AMP analogue was unmasked.3 Unidirectional ion flux measurements revealed that 293B suppressed the increase in J(sm)(Rb) induced by forskolin. This, together with the inhibition of cyclic AMP-induced anion secretion indicates that the drug blocks K+ channels, presumably both in the apical and the basolateral membrane. Forskolin caused not only inhibition of K+ absorption, but also stimulation of K+ secretion. The inhibition was diminished, but not blocked, in the presence of inhibitors of the apical H+-K+-ATPase, vanadate and ouabain. Forskolin stimulated serosal, bumetanide-sensitive Rb+ uptake, whereas mucosal ouabain/vanadate-sensitive uptake remained unaffected.4 Efflux experiments revealed that forskolin caused a redistribution of cellular K+ efflux reducing the ratio of basolateral versus apical Rb+ efflux.5 These results suggest that intracellular cyclic AMP exerts its effects on K+ transport by several mechanisms: an increase in the driving force for K+ efflux due to the depolarization induced by opening of Cl- channels, a stimulation of the basolateral uptake of K+ via the Na+-K+-Cl--cotransporter, and a decrease of the ratio of basolateral versus apical K+ conductance leading to an enhanced efflux of K+ into the lumen and a reduced K+ efflux to the serosal compartment.

Harvard Citation style: Diener, M., Hug, F., Strabel, D. and Scharrer, E. (1996) Cyclic AMP-dependent regulation of K+ transport in the rat distal colon, British Journal of Pharmacology, 118(6), pp. 1477-1487. https://doi.org/10.1111/j.1476-5381.1996.tb15563.x

APA Citation style: Diener, M., Hug, F., Strabel, D., & Scharrer, E. (1996). Cyclic AMP-dependent regulation of K+ transport in the rat distal colon. British Journal of Pharmacology. 118(6), 1477-1487. https://doi.org/10.1111/j.1476-5381.1996.tb15563.x