Abstract
Dibutyryl adenosine 3', 5'-monophosphate (dB-cAMP) stimulates the biosynthesis of 14C-dopamine from 14C-tyrosine in slices obtained from the striatum of rats. The stimulation is due to the cyclic nucleotide component of the molecule. The dB-cAMP-induced stimulation of 14C-dopamine biosynthesis occurs prior to or at the tyrosine hydroxylase step. The specific activities of labeled tyrosine and of labeled dopamine are unaltered by dB-cAMP, thereby indicating that the mechanism responsible for the stimulation of dopamine biosynthesis is not associated with changes in the labeling of the endogenous tyrosine and dopamine pools. The kinetic data show that dB-cAMP increases the Vmax but has no effect on the Km for tyrosine. These results suggest that dB-cAMP-elicited stimulation of 14C-dopamine biosynthesis might be due to an activation of tyrosine hydroxylase itself, to an inactivation of an endogenous inhibitor of the enzyme or to an increase in the levels of the cofactor. dB-cAMP also stimulates the biosynthesis of 14C- dopamine in K+-enriched medium or in Ca++-deprived medium. dB-cAMP and K+ have a cumulative effect, indicating that these two agents augment the biosynthesis of 14C- dopamine by a different mechanism. The blockade or activation of dopamine receptor did not affect the dB-cAMP-induced stimulation of dopamine biosynthesis. Thus, the stimulation of dopamine biosynthesis elicited by dB-cAMP is not influenced by changes in the receptor activity. The results of this study suggest that cAMP may play a role in the short-term regulation of dopamine biosynthesis.
Footnotes
- Received November 24, 1973.
- Accepted July 27, 1974.
- © 1974 by The Williams & Wilkins Co.
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