Ascorbic acid decreases [(3)H]dopamine binding in striatum without inhibiting dopamine-sensitive adenylate cyclase.
Ascorbic acid is found in very high concentrations in cells of neural crest origin such as the central nervous system and the adrenal gland. A variety of evidence has been marshalled to support a role for ascorbate as a chemical messenger. One of the first non-biosynthetic biochemical effects ascribed to ascorate in the CNS was its ability to inhibit dopamine-stimulated adenylate cyclase (DA-ACase) in homogenates from striata of Long Evans rats (J. Neurochem.28, 663, 1977). Using an adenylate cyclase assay based on preparative HPLC, we were unable to detect any inhibition of DA-ACase by ascorbate at concentrations as high as 1 mM. Moreover, this failure to find inhibitory effects of ascorbate on DA-ACase occurred not only when striatal homogenates from Long-Evans rats were used, but also when tissue from Sprague-Dawley rats of N.C. Board of Health mice was tested. Although ascorbate may play a neuromodulatory role, it does not appear that its effects are mediated through effects on cAMP biosynthesis. Despite our inability to detect effects of ascorbate on DA-ACase, we did confirm that ascorbate significantly altered the binding of [(3)H]dopamine to striatal membranes. Thus, it is clear that the sites binding [(3)H]dopamine that are affected by ascorbate are unlikely to be the same ones coupled to aenylate cyclase.
Schulz
D W
DW
Biological Sciences Research Center and Departments of Psychiatry and Pharmacology, University of North Carolina School of Medicine, Chapel Hill, N.C. 27514, U.S.A.
Lewis
M H
MH
Petitto
J
J
Mailman
R B
RB