Brain catecholamine content

As found with guanethidine, doses of other guanidines sufficient to cause marked depletiort of noradrenaline from tissues such as heart or spleen, fail to lower the catecholamine content of the brain or adrenals. This has been shown for j3-hydroxyphenethylguanidine (LXXXVll) [265], guanisoquin (LXVII, R = 7-Br, = H) [277], 3-phenoxypropylguanidine (LXXXV) [249],... 

It has been estimated that dopamine contributes at least 50% to the total CNS catecholamine content. A number of nemo-logical diseases are based on the activity of dopamine and examples include drug addiction, Tomette s syndrome, Parkinson s and Huntington s disease and schizophrenia. Fom major dopamine systems have heen identified in the brain. 

Adrenaline is the major component of the hormonal secretion of the adrenal medulla and in the adrenal gland noradrenaline can be regarded simply as a precursor of the active substance. In sympathetic nerves, however, catecholamine synthesis proceeds no further than noradrenaline, which exists there as a transmitter substance in its own right, with properties different from those of adrenaline. Noradrenaline and small amounts of adrenaline are present in the brain also, but in addition, certain areas of the brain contain amounts of dopamine quite out of prop>ortion to their noradrenaline content and there is suggestive evidence that dopamine has an independent neurohumoral function. The unique situation thus arises that one, or probably two of the precursors of adrenaline have specialized functions of their own. 

The enzyme L-aromatic amino acid decarboxylase (AADC, EC 4.1.1.28) lacks substrate specificity and has been considered to be involved in the formation of the catecholamines and serotonin. There are many differences in the optimal conditions for enzyme activity, including kinetics, affinity for PLP, activation and inhibition by specific chemicals, and regional differences in the distribution of DOPA and 5-HTP decarboxylation activities. Nonparallel changes in brain monoamines in the vitamin Bg-deficient rat have been reported (7-9). Brain content of dopamine and norepinephrine were not decreased during deficiency, whereas serotonin was significantly decreased. 

Figure 19 Distribution of vesicle content for potassium-stimulated release at varicosities plotted as the cubed root of catecholamine released. Plots of the percent of total events observed in the first 40 s following initiation of release vs. the cubed root of the amount of catecholamine released upon elevated potassium stimulation for (A) 17 undifferentiated PC12 cells (475 total release events) and (B) 16 differentiated PC 12 cells (156 total release events). (Reproduced from Brain Res. with permission [3].)...

The hypothalmus region was most susceptible to these changes in catecholamine biosynthesis. In spite of the observed increase in catecholamine biosynthesis in the brain and adrenals, the endogenous content of NA and DA in the brain and DA and HA in the adrenals remained unchanged . 

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