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Title: Effect of hypothalamic hormones on presynaptic dopaminergic mechanisms
Author: Shapiro, Leonie Marcia
ISNI:       0000 0001 3397 1856
Awarding Body: University of Glasgow
Current Institution: University of Glasgow
Date of Award: 1978
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The hypothalamic hormones melanostatin (MIH) and thyroliberin (TRH) have been shown by others to have a direct action on adrenergic neurons, distinct from their role in regulating the release of pituitary hormones. This present thesis examines the effect of MIH and TRH on the biosynthesis, release and oxidative deamination of dopamine in rat brain tissue preparations. Neither MIH (10-4M) nor TRH (10-4M) altered monoamine oxidase activity in tissue slices or sucrose homogenates. Autoradiographic analysis showed that there were two products of the oxidative deamination of dopamine by striatal homogenates, one of which was DOPAC. Roughly equal amounts of DOPAC and an unknown compound were formed. MIH and TRH did not alter the total amount of, or the distribution of label between, the two metabolites. Neither MIH (10-4M) nor TRH (10-4M) had any effect on the rate of dopamine synthesis by striatal homogenates. Calcium chloride (0.85 mM) stimulated dopamine synthesis by striatal synaptosomes incubated in 18.4 muM tyrosine, but neither MIH (10-4M) nor TRH (10-4M) altered the rate of dopamine synthesis. Neither peptide significantly stimulated the rate of dopamine synthesis in the presence of 0.85 mM calcium chloride. Neither MIH (10-4M) nor TRH (10-4M) altered the rate of dopamine synthesis by striatal synaptosomes in the presence of 1.70 mM calcium chloride at 1.07 muM tyrosine. Tyramine, a sympathomimetic amine, inhibited dopamine synthesis, 50% inhibition occurring at 3.3 x 10-5M. Both tyramine (10-4M) and amphetamine (10-4M) stimulated dopamine synthesis in the presence of 2 mM EDTA but the magnitude of the drug-induced stimulation varied inversely with the basal rate of dopamine synthesis. TRH (10-4M) did not stimulate dopamine synthesis under these conditions. Amphetamine (10-4M) stimulated release of dopamine from striatal synaptosomes in the presence of 1.25 mM calcium chloride and also in the presence of 2mM EDTA. MIH (10-3M) and TRH (10-3M) stimulated release of dopamine only in the presence of calcium chloride. These results suggest that MIH and TRH release dopamine from vesicular stores by exocytosis while amphetamine releases dopamine from a cytoplasmic pool regulating tyrosine hydroxylase.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available