Age-specific alterations in muscarinic stimulation of K +-evoked dopamine release from striatal slices by cholesterol and S-adenosyl- l-methionine

Abstract

The present experiments were carried out in order to test the hypothesis that age-related signal transduction (ST) deficits may occur as a result of structural changes in the membrane that are reflected partially as increased membrane microviscosity. Oxotremorine (oxo) enhancement of K +-evoked release of dopamine (K +-ERDA) was examined in superfused striatal slices from mature (6 months) and old (24 months) Wistar rats incubated (1 or 4 h, 37°C) with graded concentrations of S-adenosyl- l-methionine (SAM) or cholesterol hemisuccinate (CHO) in a modified Krebs medium. Tissue was then assessed for one of the following: (a) the degree of oxo-enhanced K +-ERDA, (b) carbachol stimulated low K m GTPase activity, or (c) alterations in membrane microviscosity. In other experiments the tissue was incubated in CHO followed by SAM (or the reverse), and oxo-enhanced K +-ERDA examined. Results indicated that SAM treatment increased all the parameters in the striatal tissue from old animals, while CHO had selective, opposite effects in the striatal tissue obtained from young animals. CHO-SAM, or the reverse, produced the same pattern of results. These results suggest that ST deficits may involve age-related structural alterations in membranes that interfere with receptor-G protein coupling/uncoupling.