Potentiation of quantal catecholamine secretion by glibenclamide: evidence for a novel role of sulphonylurea receptors in regulating the Ca(2+) sensitivity of exocytosis.
Electrochemical detection of quantal catecholamine release from PC-12 cells revealed that glibenclamide, an inhibitor of ATP-sensitive K(+) channels, potentiated Ca(2+)-dependent exocytosis evoked by raised extracellular [K(+)] and by exposure of cells to caffeine. Glibenclamide was without effect on voltage-gated Ca(2+) currents, membrane potential, or rises of [Ca(2+)](i) evoked by either raised extracellular [K(+)] or caffeine. The dependence of K(+)-evoked secretion on extracellular Ca(2+) was shifted leftward in the presence of glibenclamide, with a small increase in the plateau level of release, suggesting that glibenclamide primarily increased the Ca(2+) sensitivity of the exocytotic apparatus. Enhancement of secretion by glibenclamide was reversed by pinacidil and cromakalim, indicating that the effects of glibenclamide were mediated via an action on a sulfonylurea receptor. These results demonstrate that sulfonylurea receptors can modulate Ca(2+)-dependent exocytosis via a mechanism downstream of Ca(2+) influx or mobilization.
Institute for Cardiovascular Research, University of Leeds, Leeds LS2 9JT, United Kingdom.
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SC
Taylor
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Carpenter
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ML
Roberts
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Peers
D018528:ATP-Binding Cassette Transporters; D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology / Q000502:physiology*; D002395:Catecholamines / Q000378:metabolism*; D019806:Cromakalim / Q000494:pharmacology; D004533:Egtazic Acid / Q000494:pharmacology; D004563:Electrochemistry; D005089:Exocytosis / Q000187:drug effects / Q000502:physiology*; D005905:Glyburide / Q000494:pharmacology*; D007700:Kinetics; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D016716:PC12 Cells; D018408:Patch-Clamp Techniques; D020110:Pinacidil / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D024661:Potassium Channels, Inwardly Rectifying; D011789:Quantum Theory; D051381:Rats; D011955:Receptors, Drug / Q000187:drug effects / Q000502:physiology*; D064233:Sulfonylurea Receptors; D014044:Tolbutamide / Q000494:pharmacology
D018528:ATP-Binding Cassette Transporters; D002395:Catecholamines; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D011955:Receptors, Drug; D064233:Sulfonylurea Receptors; D019806:Cromakalim; D002110:Caffeine; D004533:Egtazic Acid; D020110:Pinacidil; D014044:Tolbutamide; D011188:Potassium; D005905:Glyburide; D002118:Calcium