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. 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. Unidirectional ion flux measurements revealed that 293B suppressed the increase in JRbsm 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. Efflux experiments revealed that forskolin caused a redistribution of cellular K+ efflux reducing the ratio of basolateral versus apical Rb+ efflux. 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.

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Eicosanoids are involved in the mediation of inflammatory and allergic processes in the gut. In order to evaluate a potential beneficial effect of the diet, the effect of mediators of inflammation and of a sensitization against egg albumin on anion secretion across the colon was tested using rats fed on a diet containing 15% fish oil as compared to 15% olive oil as donor animals. Feeding on a fish oil diet significantly reduced the response to bradykinin or phospholipase C, known agonist of prostaglandin-induced secretion, by about 50%. The increase in short-circuit current (Isc) induced by the phospholipase A2 stimulator, melittin, or by distension of the gut wall were only insignificantly inhibited by 15-30%. Administration of egg albumin to the mucosas from animals sensitized against egg albumin induced an indomethacin- and tetrodotoxin-sensitive increase in Isc. This response was, however, only insignificantly (30%) reduced by the fish oil diet. In conclusion, the effect of fish oil diet depends on the stimulus used for activation of prostaglandin release. This suggested that different pools of arachidonic acid are differentially affected by the diet or that certain stimuli for phospholipases are strong enough to overcome the effect of a reduced substrate availability. Consequently, a diet rich in polyunsaturated n-3 fatty acids may only play an adjuvant role for the therapy of inflammatory or allergic intestinal diseases.

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