Active Potassium Transport Across Guinea-Pig Distal Colon: Action of Secretagogues

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1. Adrenaline (5 microM) stimulated a K+ secretory current by 2-2 microequiv h-' cm2 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 ,microequiv h- cmM2, respectively. Serosal addition of bumetanide completely inhibited this K+ secretion but blocked only -70% of Cl- secretion. The bumetanide-insensitive Cl- secretory current was dependent on the presence of Cl- and HC03- in the bathing solutions.

3. Stimulation of electrogenic K+ secretion by PGE2 occurred with a half-maximal concentration of 4 nm, an affinity -300 times higher than that for stimulation of Cl-secretion by PGE2.

4. Forskolin (10 microM) stimulated Cl- secretion by 4-9 microequiv h-' cm2. The apparent K+ secretory rate was increased by only 1-5 microequiv h-1 cm2. 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.

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