Selective inhibition by ethanol of glutamate-stimulated cyclic GMP production in primary cultures of cerebellar granule cells.
In primary cultures of cerebellar granule cells of the rat, the accumulation of cyclic GMP was stimulated by glutamate, acting at the N-methyl-D-aspartate recognition site, and by atrial natriuretic factor. The response to glutamate was calcium-dependent, while the response to atrial natriuretic factor was not. Ethanol inhibited the accumulation of cyclic GMP in response to both glutamate and atrial natriuretic factor. However, the response to glutamate was much more sensitive to ethanol, with 30-40% inhibition occurring at 50 mM ethanol. Substantial inhibition of the response to atrial natriuretic factor was observed only at concentrations of ethanol of 200 mM or larger. The data suggest that a major site of action of ethanol in inhibiting the accumulation of cyclic GMP is the coupling of the glutamate receptor to soluble guanylate cyclase. The effect of ethanol on agonist-activated activity of guanylate cyclase may contribute to the pharmacological action of ethanol in vivo.
Hoffman
P L
PL
National Institute on Alcohol Abuse and Alcoholism, Division of Intramural Clinical and Biological Research, Bethesda, Maryland 20892.
Moses
F
F
Tabakoff
B
B
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000494:pharmacology; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D006152:Cyclic GMP / Q000096:biosynthesis*; D003594:Cytoplasmic Granules / Q000187:drug effects / Q000378:metabolism; D000431:Ethanol / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists; D005971:Glutamates / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D018691:Excitatory Amino Acid Antagonists; D005971:Glutamates; D000431:Ethanol; D009320:Atrial Natriuretic Factor; D006152:Cyclic GMP