The purpose of this project is to study, in alcoholic and control subjects, the effects of ethanol on calcium metabolic functions that control free intracellular calcium concentration ([Ca++f]i) in platelets. The platelet has been used as a peripheral model for biochemical and physiological processes in central nervous system nerve endings because of several functional similarities, including the role of calcium as a second messenger and the storage and release of neurotransmitter. The intracellular free calcium concentration in platelets and nerve endings regulates many intracellular biochemical and physiological functions. Ethanol has been shown to affect some aspects of calcium metabolism in cellular function, such as intracellular binding of calcium in synaptosomes, voltage dependent influx of calcium into nerve endings, uptake of calcium into mitochondria and endoplasmic reticulum, extractability of calmodulin from platelet membranes with EGTA, and calcium-dependent neurotransmitter release. A long-term objective of this project will be to understand the effects of ethanol on calcium-mediated cellular functions of alcoholics. The experiments in the project will use platelets from alcoholic and control subjects to test the hypothesis that acute and chronic ethanol exposure alters neurotransmitter release by effects on calcium metabolic functions that control [Ca++f]i. The release of neurotransmitter by nerve endings and platelets is a function of the intracellular free calcium concentration. The calcium metabolic functions we will study regulate the free intracellular calcium concentration of platelets. The research subjects for these experiments will be alcoholics diagnosed by certain biochemical procedures as well as DSM-III criteria for alcoholism. Blood samples will be drawn from control subjects, tolerant alcoholic subjects, and non-tolerant alcoholic subjects. The tolerant alcoholics will be admitted to the Alcoholic Treatment Unit of the VA Hospital. Control subjects will be age- and culture-matched male adults from the San Antonio community who have been carefully screened, especially regarding their ethanol consumption.
| Tan, C H; Javors, M A; Seleshi, E et al. (1990) Effects of lithium on platelet ionic intracellular calcium concentration in patients with bipolar (manic-depressive) disorder and healthy controls. Life Sci 46:1175-80 |
