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

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 90; no. 4; pp. 1340 - 1344
• Main Authors: Bernardi, Henri, De Weille, Jan R., Epelbaum, Jacques, Mourre, Christiane, Amoroso, Salvatore, Slama, Annie, Fosset, Michel, Lazdunski, Michel
• Format: Journal Article
• Language: English
• Published: Washington, DC National Academy of Sciences of the United States of America 15.02.1993; National Acad Sciences; National Academy of Sciences
• Subjects: Adenosine Diphosphate - pharmacology; Adenosine Triphosphate - pharmacology; Affinity Labels - metabolism; Animals; Anterior pituitary; B lymphocytes; Binding sites; Biological and medical sciences; Calcium - metabolism; Cells, Cultured; Computer Science; Diazoxide - pharmacology; Electrophysiology; Female; Fundamental and applied biological sciences. Psychology; Glipizide - pharmacology; Glyburide - metabolism; Growth Hormone - metabolism; Growth hormones; Hypoglycemic agents; Hypoglycemic Agents - pharmacology; Hypothalamus. Hypophysis. Epiphysis. Urophysis; Kinetics; Life Sciences; Membrane Potentials - drug effects; Microsomes; Morphology. Functional localizations; Oligomycins - pharmacology; Pancreatic cells; Pituitary gland; Pituitary Gland, Anterior - drug effects; Pituitary Gland, Anterior - metabolism; Pituitary Gland, Anterior - physiology; Potassium Channels - drug effects; Potassium Channels - physiology; Rats; Receptors, Drug - metabolism; Secretion; Sulfonylurea Compounds - pharmacology; Vertebrates: endocrinology; Endocrine gland; Rat; Secretion; STH; Rodentia; Electrophysiology; Ionic channel; Adenohypophysis; Protein hormone; Vertebrata; Regulation(control); Mammalia; Sulfonylureas; Pituitary gland; ATP; Potassium
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.90.4.1340

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.