Ion channel effects of antidiabetic sulfonylureas.
ATP-sensitive potassium channels are found in a number of different tissues where they play distinct physiological functions. In all these tissues they are blocked by antidiabetic sulfonylureas. In endocrine cells they regulate the secretion of hormones such as insulin, prolactin, and growth hormone. They influence the excitability of cardiac, skeletal, and vascular smooth muscle. They play an important role in connecting changes of extracellular glucose levels in the brain to changes of neurotransmitter release. They are of particular importance during hypoxia and ischemia in both the heart and the brain, where they intervene to reduce or delay cell death. Both electrophysiological and pharmacological evidence points towards ATP-sensitive potassium channels making up a class of ion channels with tissue-specific as well as functional differences. Particularly, these different classes of ATP-sensitive K+ channels have different sensitivities to antidiabetic sulfonylureas. There is probably considerable scope for the development of specific products to either enhance or inhibit the action of these ion channels in different tissues under different pathological conditions.
Institut de Pharmacologie Moléculaire et Cellulaire, CNRS, Valbonne, France.
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Lazdunski
D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007515:Islets of Langerhans / Q000502:physiology; D009206:Myocardium / Q000378:metabolism; D015221:Potassium Channels / Q000187:drug effects* / Q000502:physiology; D013453:Sulfonylurea Compounds / Q000494:pharmacology*
D007004:Hypoglycemic Agents; D015221:Potassium Channels; D013453:Sulfonylurea Compounds; D000255:Adenosine Triphosphate