PRENATAL ETHANOL EXPOSURE REDUCES PHOSPHOINOSITIDE HYDROLYSIS STIMULATED BY QUISQUALATE IN RAT CEREBELLAR GRANULE CELL-CULTURES

Prenatal ethanol exposure-induced alteration in poly-phosphoinositide (PPI) hydrolysis stimulated by excitatory amino acids (EAA) was studie d in rat cerebellar granule cells previously labeled with [H-3]myoinos itol. The prenatal exposure to ethanol was achieved via maternal consu mption of a Sustacal (chocolate flavored) liquid diet containing eithe r 5% ethanol (w/v, 35% of calories) or isocaloric sucrose (pair-fed) s ubstituted for ethanol from gestation d 11 until the day of parturitio n. The ionotropic glutamate receptor agonists, N-methyl-D-aspartate, k ainate or pha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) (1 00 mu M each) induced a two- to fourfold increase in PPI hydrolysis ov er the basal level, regardless of the liquid dietary treatment. Stimul ation with quisqualate (QA), an agonist activating both metabotropic a nd ionotropic glutamate receptors, resulted in a much stronger and dos e-dependent response in PPI hydrolysis and exposure in utero to ethano l significantly reduced this response. Tetrodotoxin, 6-cyano-7-nitroqu inoxaline-2, 3-dione (CNQX), or )-3-(2-carboxypiperazine-4-yl)-propyl- 1-phosphonic acid (CPP) had no effect on QA-stimulated PPI hydrolysis nor on the suppression of this hydrolysis by ethanol. Exposure in uter o to ethanol did not affect PPI hydrolysis stimulated by a selective m etabotropic glutamate receptor agonist, trans-(+/-)-1-amino-1,3-cyclop entanedicarboxylic acid (t-ACPD). Although the PPI hydrolysis stimulat ed by t-ACPD could be blocked by (RS)-alpha-methyl-4-carboxyphenylglyc ine (MCPG), an antagonist of the metabotropic glutamate receptor, MCPG was incapable of affecting QA-induced PPI hydrolysis and the suppress ive effects of prenatal ethanol exposure on this hydrolysis. Taken tog ether, the data suggest that the long-lasting suppressive effects of p renatal ethanol exposure on QA-stimulated PPI hydrolysis in cerebellar granule cell cultures is through a metabotropic QA receptor pathway t hat may be different from the one activated by t-ACPD.