Metabolism of Catecholamines in the Developing Spinal Cord of the Rat

Abstract

The metabolism of 3,4-dihydroxyphenylethylamine (DA, dopamine) and norepinephrine (NE) both normally, and after the administration of levo-3,4-dihydroxyphenylalanine (L-DOPA), has been studied in several regions of the developing spinal cord of the rat from fetal day (FD) 16 to the young adult stage. During late fetal (from FD 16) and most of neonatal life [to neonatal day (ND) 20], dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) were either just detectable or present in very low concentration in all regions in the untreated developing rat. However, the developing spinal cord possesses an enormous capacity to metabolize the large amounts of DA synthesized from injected L-DOPA. At the end of 1 h after 100 mg/kg i.p. of L-DOPA, DOPAC and HVA are 54 +/- 14 (n = 5) and 16 +/- 5 (n = 5) nmol/g, respectively, in the thoracic zona intermedia in the 12-h-old (ND 0.5) rat. This metabolic capability is already highly developed as early as FD 16, peaks during the first half of neonatal life (ND 4 for DOPAC, and ND 15 for HVA), and is considerably reduced toward the end of neonatal life (approximately ND 28) and in the young adult. Control experiments suggest that a substantial part of this synthesis (from L-DOPA) and metabolism of DA occurs in elements other than the descending monoaminergic nerve fibers. By comparison, the synthesis and metabolism of NE develop more slowly, peak in the latter half of neonatal life, and then decline to the level found in the young adult.(ABSTRACT TRUNCATED AT 250 WORDS)

L‐DOPA and 5‐HTP modulation of air‐stepping in newborn rats

“…In contrast, stable spinal levels of 5-HTP are observed in 5-HTP and 5-HTP/L-DOPA conditions, suggesting that the AADC would have a higher affinity for 5-HTP than L-DOPA. This result echoes data reporting that 5-HTP and L-DOPA certainly compete in cells expressing AADC for the production of both 5-HT and dopamine, respectively (Butcher & Engel, 1969;Everett & Borcherding, 1970;Ng et al 1970;Andén & Fuxe, 1971;Commissiong & Sedgwick, 1979;Commissiong, 1984Commissiong, , 1985. This is in line with results in the brain showing that the administration of L-DOPA induced ectopic efflux of dopamine from serotonergic neurons (Navailles et al 2010(Navailles et al , 2011Miguelez et al 2016), while the administration of 5-HTP induced 5-HT synthesis and release from catecholaminergic neurons (Stamford et al 1990).…”

“…This result echoes data reporting that 5‐HTP and L‐DOPA certainly compete in cells expressing AADC for the production of both 5‐HT and dopamine, respectively (Butcher & Engel, 1969; Everett & Borcherding, 1970; Ng et al . 1970; Andén & Fuxe, 1971; Commissiong & Sedgwick, 1979; Commissiong, 1984, 1985). This is in line with results in the brain showing that the administration of L‐DOPA induced ectopic efflux of dopamine from serotonergic neurons (Navailles et al .…”

Development of Monoaminergic Neurotransmitters in Fetal and Postnatal Rat Brain: Analysis by HPLC with Electrochemical Detection

“…Whether the monoamines measured in total brain during gestational life originate only from the fetal CNS is doubtful. Part of the metabolites measured in the fetal brain are possibly derived from monoamines or their precursors, which have a maternal origin and have crossed the placental barrier and are then further metabolized in the fetus (Commissiong, 1985). ~-3,4-Dihydroxyphenylalanine, of maternal origin, can easily cross the placenta and fetal blood-brain bamer and is immediately transformed to DOPAC, without the formation of DA, NE, or E. This alternative pathway would permit the accumulation of DOPAC and HVA in the fetus without reflecting catecholaminergic neurotransmission.…”

Limiting Monoamines Degradation Increases L-DOPA Pro-Locomotor Action in Newborn Rats

“…Indeed, exogenous L-DOPA does not impact, or only marginally, the tissue content of noradrenaline even if it is a metabolic precursor and despite the concomitant increase in dopamine tissue content. As explained above, however, the raise in dopamine tissue content induced by L-DOPA witnesses a high rate of decarboxylation of L-DOPA in several cellular species, and the contribution of noradrenergic terminals in this increase is probably marginal [20,43]. In addition, an excess of dopamine or other trace amines in the cytosol of noradrenergic terminals might induce a flush of noradrenaline away from the vesicle of exocytosis, thereby exposing noradrenaline to degrading enzymes [44].…”