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

Abstract

1. Adrenaline (5 microM) 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 E2 (PGE2, 2 microM) 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 approximately 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 PGE2 occurred with a half-maximal concentration of 4 nM, an affinity approximately 300 times higher than that for stimulation of Cl- secretion by PGE2. 4. Forskolin (10 microM) 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 (ISC) was apparent and of the same size as that stimulated by PGE2. 5. Addition of the Ca2+ ionophore A23187 (10 microM), in the presence of indomethacin (1 microM) 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 ISC, 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.