ATP-Modulated K+Channels Sensitive to Antidiabetic Sulfonylureas are Present in Adenohypophysis and are Involved in Growth Hormone Release

The adenohypophysis contains high-affinity binding sites for antidiabetic sulfonylureas that are specific blockers of ATP-sensitive K+channels. The binding protein has a Mrof 145,000 ± 5000. The presence of ATP-sensitive K+channels (26 pS) has been demonstrated by electrophysiological techniques. Intracellular perfusion of adenohypophysis cells with an ATP-free medium to activate ATP-sensitive K+channels induces a large hyperpolarization (≈ 30 mV) that is antagonized by antidiabetic sulfonylureas. Diazoxide opens ATP-sensitive K+channels in adenohypophysis cells as it does in pancreatic β cells and also induces a hyperpolarization (≈ 30 mV) that is also suppressed by antidiabetic sulfonylureas. As in pancreatic β cells, glucose and antidiabetic sulfonylureas depolarize the adenohypophysis cells and thereby indirectly increase Ca2+influx through L-type Ca2+channels. The K+channel opener diazoxide has an opposite effect. Opening ATP-sensitive K+channels inhibits growth hormone secretion and this inhibition is eliminated by antidiabetic sulfonylureas.