[Effect of TRH and histidyl-proline diketopiperazine (cyclo(His-Pro] on catecholamine secretion]

The effects of TRH and its metabolite, histidyl-proline diketopiperazine (cyclo(His-Pro] on catecholamine metabolism in the central nervous system, peripheral tissues and plasma were examined in adult and young Wistar rats aged 3 weeks. The intravenous administration of 50 micrograms of TRH produced an increase in plasma epinephrine, cerebral dopamine and a reciprocal decrease in norepinephrine and dopamine in diencephalon and midbrain. In contrast, 50 micrograms of cyclo(His-Pro) induced a rise in plasma dopamine and a decrease of dopamine in cerebellum, pons and medulla oblongata. After intraperitoneal injection of 3 mg of alpha-methyl-p-tyrosine, which blocked re-uptake of catecholamines in synapses, intrathecal administration of 30 ng TRH accelerated 2 times metabolic turnover of norepinephrine and dopamine in cerebral hemisphere, diencephalon and midbrain as well as norepinephrine turnover in cerebellum, pons, medulla oblongata, heart and brown adipose tissue. Consecutive intrathecal administration of TRH for 6 days enhanced cerebral catecholamine content. These results indicate that (1) TRH accelerates metabolic rate of catecholamine in the central nervous system as well as peripheral tissues, and (2) TRH acts on both noradrenergic and dopaminergic neurons in cerebral hemisphere, diencephalon and midbrain, whereas cyclo(His-Pro) acts mainly on dopaminergic neurons in cerebellum, pons and medulla oblongata.