Synthesis of Dopamine by Non-Dopaminergic Neurons of the Rat Tuberoinfundibular System during Ontogeny

Abstract—In the early 2000s, it was shown that dopamine is synthesized not only by dopaminergic neurons that possess the necessary set of enzymes, tyrosine hydroxylase and aromatic L-amino acid decarboxylase (AAD), but also by non-dopaminergic (monoenzymatic) neurons containing one of the enzymes. In this case, L-3,4-dihydroxyphenylalanine (L-DOPA), which is synthesized in neurons containing tyrosine hydroxylase, is transferred to neurons containing AAD, where dopamine is synthesized. The evidence for cooperative dopamine synthesis in our previous studies was a decrease in the total dopamine synthesis during incubation of a suspension of neurons of the tuberoinfundibular system (TIS) of fetuses or TIS slices from adult rats in the presence of a neutral amino acid that is a competitive inhibitor of the membrane L-DOPA carrier. In this work, the previously applied methodological approach was improved by using only sections of TIS and 2-amino-2-norbornanecarboxylic acid, a synthetic non-metabolizable L-DOPA membrane carrier inhibitor. This made it possible to confirm the presence of cooperative dopamine synthesis in TIS in fetuses and adult rats, and to obtain additional evidence of this synthesis in the form of an increase in the intercellular content of L-DOPA during inhibition of its membrane carrier. In addition, using an improved method we quantitatively characterized the synthesis of dopamine by nondopaminergic neurons and compared it in fetuses and adult rats. It was shown that the proportion of cooperative dopamine synthesis from the total dopamine synthesis by monoenzymatic and dopaminergic neurons in TIS in rat fetuses is 1.8 times higher than in adult animals. A six-fold increase in the synthesis of dopamine by rat TIS monoenzymatic neurons from the end of the prenatal period to adulthood are of particular interest from the standpoint of the functional role of dopamine produced by monoenzymatic neurons. Thus, in ontogeny, the proportion of dopamine synthesis by nondopaminergic monoenzymatic neurons in the general synthesis of dopamine is significantly reduced and the absolute value of cooperative dopamine synthesis increases by many times.