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Reduction of Dopamine Synthesis Inhibition by Dopamine Autoreceptor Activation in Striatal Synaptosomes with In Vivo Reserpine Administration
Author(s) -
Tissari Anja H.,
Lillgäls Monica S.
Publication year - 1993
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.1471-4159.1993.tb03559.x
Subject(s) - reserpine , autoreceptor , apomorphine , chemistry , dopamine , bromocriptine , endocrinology , medicine , dopamine agonist , pergolide , agonist , sulpiride , lisuride , synaptosome , pharmacology , dopaminergic , biology , in vitro , prolactin , receptor , biochemistry , hormone
In an attempt to clarify the mechanisms by which dopamine (DA) autoreceptor activation inhibits DA synthesis, the efficacy and potency of the D 2 DA agonists bromocriptine, lisuride, and pergolide, and the D 1 ,‐D 2 DA agonist apomorphine were studied in rat striatal synapto‐ somes, in which the rate of DA synthesis (formation of 14 CO 2 from l ‐[1– 14 C]tyrosine) was increased 103% by treating the animals from which the synaptosomes were obtained with reserpine (5 mg/kg i.p. twice, 24 and 2 h before they were killed), using the striatal total homogenate as the standard synaptosomal preparation. The increase in DA synthesis evoked by reserpine was additive with that produced by treatment of the synaptosomes with dibutyryl cyclic AMP, suggesting that, not a cyclic AMP‐dependent, but possibly a Ca 2+ ‐dependent mechanism was involved. The DA agonists showed a concentration‐dependent inhibition of DA synthesis in the control synaptosomes, which was antagonized by the selective D 2 DA antagonist (‐)‐sulpiride. In the synaptosomes with increased rate of DA synthesis obtained from the rats treated with reserpine, the concentration‐response curves of DA synthesis inhibition for the other DA agonists were shifted to the right, and the effect of bromocriptine was completely eliminated, whereas bromocriptine antagonized the effect of apomorphine. The increased rate of DA synthesis was not preserved in the striatal P 1 + P 2 fraction obtained from the reserpine‐treated rats, but the effects of the DA agonists were still reduced to the same degree as those in the total homogenate. (‐)‐Sulpiride did not enhance DA synthesis in synaptosomes from the reserpine‐ treated rats. The results presented indicate that the reduced effect of the DA agonists in synaptosomes from the reserpine‐treated rats was not due to endogenous DA occupying the DA autoreceptors. Because it is known from the literature that reserpine in vivo increases impulse activity in DA neurons and, as a result, increases the Ca 2+ concentration, these results suggest that the effect of DA agonists was reduced because DA autoreceptors may normally control DA synthesis by decreasing the free intraneuronal Ca 2+ concentration, and consequently, the Ca 2+ ‐dependent phosphorylation of tyrosine hydroxylase.