BIOCHEMICAL EVALUATION OF ADRENERGIC FUNCTION

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Measurement of levels of norepinephrine (NE), its metabolites, and precursors in plasma, urine, and cerebrospinal fluid have been developed and are being applied to studies of changes of these compounds in patients with various disorders of the autonomic nervous system and in rats after administration of drugs which alter synthesis, storage, release metabolism, or uptake of NE in sympathetic nerves. Drugs such as desipramine (or cocaine) which block uptake, enhance apparent release of norepinephrine into the circulation and diminish formation of its deaminated metabolites, DHPG and MHPG. L-DOPA is formed in the sympathetic neurones and overflows into the blood. It may be an important source of extraneuronal dopamine and act as a neurohumoral agent. Patients with orthostatic hypotension have parallel decreases in excretion of homovanillic acid (HVA), the major metabolite of dopamine, and norepinephrine metabolites (MHPG and VMA). A similar relationship holds in animals and humans treated with debrisoquin to inhibit peripheral catecholamine metabolism. Using monkeys treated with MPTP to destroy central dopaminergic neurones, we have established the validity of extrapolating the regression line relating HVA to MHPG to measure the brain HVA production. This has been done in both urine and plasma of monkeys. A means of rapid enzymatic conversion of 18F-dopa to 18F-dopamine has been developed. The 18F-dopamine is to be administered as a precursor of endogenous 18F-norepinephrine to study by PET scanning the peripheral sympathetic neurones in various disease states.