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 M(r) of 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 (approximately 30 mV) that is antagonized by antidiabetic sulfonylureas. Diazoxide opens ATP-sensitive K+ channels in adenohypophysis cells as it does in pancreatic beta cells and also induces a hyperpolarization (approximately 30 mV) that is also suppressed by antidiabetic sulfonylureas. As in pancreatic beta 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.
Bernardi
H
H
Institut de Pharmacologie Moléculaire et Cellulaire, Valbonne, France.
De Weille
J R
JR
Epelbaum
J
J
Mourre
C
C
Amoroso
S
S
Slama
A
A
Fosset
M
M
Lazdunski
M
M
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000345:Affinity Labels / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D003981:Diazoxide / Q000494:pharmacology; D005260:Female; D005913:Glipizide / Q000494:pharmacology; D005905:Glyburide / Q000378:metabolism*; D013006:Growth Hormone / Q000378:metabolism*; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007700:Kinetics; D008564:Membrane Potentials / Q000187:drug effects; D009840:Oligomycins / Q000494:pharmacology; D010903:Pituitary Gland, Anterior / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D011955:Receptors, Drug / Q000378:metabolism; D013453:Sulfonylurea Compounds / Q000494:pharmacology*
D000345:Affinity Labels; D007004:Hypoglycemic Agents; D009840:Oligomycins; D015221:Potassium Channels; D011955:Receptors, Drug; D013453:Sulfonylurea Compounds; C067662:glibenclamide receptor; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D013006:Growth Hormone; D003981:Diazoxide; D005905:Glyburide; D002118:Calcium; D005913:Glipizide