CNS 3-methoxy-4-hydroxyphenylglycol: its peripheral assessment by isotopic dilution and theoretical significance

An isotope dilution model for the peripheral measurement of CNS catecholamine metabolism was examined in rabbits. 3H-norepinephrine (3H-norepinephrine (3H-NE) infusions were performed on rabbits before and after central sympathectomy via intraventricular 6-hydroxydopamine (6-OHDA) treatment. Urine samples were obtained 72 hr after 3H-NE infusion and analysed for specific activities (SAs) of 3-methoxy-4-hydroxyphenylglycol (MHPG) and 3-methoxy-4-hydroxymandelic acid (VMA). The SA of MHPG was lower than that of VMA in all animals suggesting a source of unlabelled MHPG. The difference between the SAs of VMA and MHPG was abolished when the brain MHPG was markedly lowered by 6-OHDA injections. In animals which received 6-OHDA but retained moderate levels of brain MHPG, the difference between SAs of VMA and MHPG was maintained. The proposed model is able to predict and differentiate between rabbits that have severe depletion of CNS catecholamines and normal controls. The results suggest important relationships between CNS and peripheral NE metabolism and the compensatory capacity of the CNS to insult.