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Quinolinic Acid Stimulates Somatostatin Gene Expression in Cultured Rat Cortical Neurons
Author(s) -
Patel Shutish C.,
Papachristou Dimitrios N.,
Patel Yogesh C.
Publication year - 1991
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1991.tb11423.x
Subject(s) - quinolinic acid , neuropeptide y receptor , medicine , endocrinology , nmda receptor , agonist , glutamate receptor , biology , somatostatin , receptor , neuropeptide , amino acid , biochemistry , tryptophan
Abstract: Striatal atrophy in Huntington's disease (HD) is characterized by selective preservation of a subclass of neurons colocalizing NADPH‐diaphorase (NADPH‐d), somatostatin (SS), and neuropeptide Y (NPY), which have been reported to show three‐ to fivefold increases in SS‐like immunoreactivity (SSLI) and NPY content. Since HD brain is capable of producing excessive quantities of the excitotoxin quinolinic acid (Quin), an N ‐methyl‐D‐aspartate (NMDA) receptor agonist, and since experimental Quin lesions show neuronal loss with sparing of NADPH‐d/SS/NPY neurons, it has been suggested that Quin may be important in the pathogenesis of HD. In the present study we determined whether Quin stimulates SS gene function in cultured cortical cells known to be rich in NADPH‐d/SS/NPY neurons. Cultures of dispersed fetal rat cortical cells were exposed to Quin (1 and 10 m M ) with or without (‐)‐2‐amino‐5‐phosphon‐ovaleric acid (APV; 0.5 m M ), an NMDA receptor antagonist, NMDA (0.2 and 0.5 m M ), and glutamate (Glu; 0.5 m M ). Medium and cellular SSLI was determined by radioimmunoassay and SS mRNA by Northern analysis with a cRNA probe. Quin induced significant ( p < 0.01) 1.6‐ and 2.5‐4 fold increases in SSLI and SS mRNA accumulation, respectively, which were abolished by APV. Release of SSLI into the culture medium was stimulated two‐ to fivefold by Quin over a 2‐ to 20‐h period. The increase in SS mRNA produced by Quin was time and dose dependent. A similar dose‐dependent increase in SS mRNA comparable with that observed with Quin was induced by NMDA. These increases were selective for SS mRNA and were not accompanied by any change in β‐actin mRNA. By contrast, glutamate at the single dose tested was without effect on both SSLI and SS mRNA. These results demonstrate that Quin induces a selective NMDA receptor‐mediated stimulation of SS gene expression and SS biosynthesis in vitro and suggest a similar mechanism for the augmented striatal SSLI in HD.