The development of cholesterol gallstones involves alterations in the relationship of the amount of cholesterol, phospholipid and bile salts present in bile resulting in bile becoming supersaturated with cholesterol. Cholesterol crystal formation then occurs and aggregation of crystals results in macro stone formation. During the crystalline and early stages of gallstone formation increased absorption of sodium and water occurs which is believed to contribute to the formation of stones by potentially increasing the concentration of crystals and nucleating factors. The proposed research is directed at determining the mechanisms by which supersaturated bile increase gallbladder absorption. The absorption of water is dependent on the transport of sodium which is dependent on the function of various Na+/H+ exchangers. The activity of the Na/HE is regulated by a number of factors which possibly include cyclic nucleotides and calcium. The proposed research intends to determine if lithogenic bile increases gallbladder absorption and the activity of the second messenger system and if these alterations are necessary for gallstone formation. The research will determine the mechanisms of sodium absorption, if it is regulated by the cyclic AMP/ Ca++ second messenger system and if these alterations accompany cholesterol gallstone formation in the cholesterol fed prairie dog.
