INTRACELLULAR TARGETS FOR ANTIDIABETIC SULFONYLUREAS AND POTASSIUM CHANNEL OPENERS

Antidiabetic sulfonylureas and potassium channel openers affect the ac tivity of the ATP-regulated potassium channel (K-ATP channel) present in the plasma membrane of various cells. This causes a broad spectrum of physiological responses, including the modulation of insulin releas e from pancreatic B-cells and the relaxation of smooth muscle. Recentl y, new targets for antidiabetic sulfonylureas and potassium channel op eners were found in membranes of organelles, such as mitochondria and zymogen-and insulin-containing granules. By acting on these targets, t he drugs modulate, independently of K-ATP channel activity, insulin re lease from pancreatic B-cells, and they regulate K+ transport in mitoc hondria and zymogen granules. The interaction of sulfonylureas and pot assium channel openers with intracellular targets gives additional bas ic information about their properties. Additionally, these studies cou ld be important because of the medical applications of sulfonylureas a nd potassium channel openers. (C) 1997 Elsevier Science Inc.