Intracellular targets for antidiabetic sulfonylureas and potassium channel openers.

Antidiabetic sulfonylureas and potassium channel openers affect the activity 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 release from pancreatic B-cells and the relaxation of smooth muscle. Recently, new targets for antidiabetic sulfonylureas and potassium channel openers were found in membranes of organelles, such as mitochondria and zymogen- and insulin-containing granules. By acting on these targets, the drugs modulate, independently of K(ATP) channel activity, insulin release from pancreatic B-cells, and they regulate K+ transport in mitochondria and zymogen granules. The interaction of sulfonylureas and potassium channel openers with intracellular targets gives additional basic information about their properties. Additionally, these studies could be important because of the medical applications of sulfonylureas and potassium channel openers.