Active potassium transport across guinea-pig distal colon: Action of secretagogues

1. Adrenaline (5 mu M) stimulated a K+ secretory current by 2.2 mu equiv h(-1) cm(-2) in isolated guinea-pig distal colonic epithelium. This secretory activity was inhibited entirely by addition of the loop diuretic bumetanide to the serosal solution. On-going K+ uptake via the absorptive pathway was unaltered by these changes. 2. Prostaglandin E(2) (PGE(2), 2 mu M) stimulated electrogenic K+ secretion and Cl- secretion by 3.0 and 3.6 mu equiv h(-1) cm-(2), respectively. Serosal addition of bumetanide completely inhibited this K+ secretion but blocked only similar to 70% of Cl- secretion. The bumetanide-insensitive Cl- secretory current was dependent on the presence of Cl- and HCO3- in the bathing solutions. 3. Stimulation of electrogenic K+ secretion by PGE(2) occurred with a half-maximal concentration of 4 nM, an affinity similar to 300 times higher than that for stimulation of Cl- secretion by PGE(2). 4. Forskolin (10 mu M) stimulated Cl- secretion by 4.9 mu equiv h(-1) cm(-2). The apparent K+ secretory rate was increased by only 1.5 mu equiv h(-1) cm(-2). A bumetanide-insensitive short-circuit current (I-SC) was apparent and of the same size as that stimulated by PGE(2). 5. Addition of the Ca2+ ionophore A23187 (10 mu M), in the presence of indomethacin (1 mu M) to reduce prostaglandin production, inhibited the K+ absorptive pathway by 40% and concurrently stimulated a small rate of electrogenic K+ secretion. 6. Active K+ absorption was inhibited by the addition of ouabain, omeprazole or SCH28080 to the mucosal solution. Both omeprazole and SCH28080 also stimulated a small negative I-SC, consistent with electrogenic K+ secretion. 7. Association of K+ absorption, K+ secretion and Cl- secretion is indicated by similarities in transport mechanism and by secretagogue regulation. In particular, maximal rates of K+ secretory current require uptake via apical membrane K+ pumps. Such interrelations support a common cellular locus for these ion transport pathways.