One of the best documented effects of ethanol exposure at the cellular level is fluidization of biological membranes. Potential consequences of fluidization of cell membranes are altered receptor protein conformations, altered membrane-bound enzyme systems, and, especially, altered conductances to ions. Any of these potential consequences of ethanol exposure could be responsible for the well documented observations of ethanol-induced alterations in endocrine activity. We have designed a unique dispersed-cell perifusion system with semi-automated radioimmunoassays (RIAs) for state-of-the-art monitoring of hormone secretion. Recently, we observed that exposure of mouse pituitary neurointermediate lobe cells to 17 mM ethanol provoked an immediate inhibition of secretion of Beta-endorphin-like (Beta-EP) and Alpha-melanocyte-stimulating hormone-like (Alpha-MSH) immunoreactivity. The inhibition continued for the duration of ethanol exposure. Secretion rates returned to baseline immediately upon termination of exposure. We have extended this observation to another cell type of the APUD-series, anterior pituitary corticotrophs. The global hypothesis of this proposal is that ethanol alters the secretory activity of cell by alteration of K+, Na+, Ca++, or other ion conductance, by altering receptor conformation, and/or by altering membrane-bound enzyme conformation. These changes at the cell membrane may be the functional counterparts of the reported fluidizing effects of ethanol.
The specific aims of this proposal are directed at 1) characterizing further the direct effects of ethanol on mNIL; 2) determining which of the above possible consequences of membrane fluidization effect the observed alterations in secretion; and 3) determining the generality of these observations in other endocrine cells.
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