Activity of tryptophan hydroxylase and content of indolamines in discrete brain regions after a long-term hypoxic exposure in the rat.
The influence of long-term hypoxia (10% O2, 14 days) on in vivo activity of tryptophan hydroxylase and on 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) concentration in discrete brain regions of rats was assessed. The activity of tryptophan hydroxylase was determined through 5-hydroxytryptophan accumulation (5-HTPacc) following the administration of NSD 1015. The 5-HTPacc was significantly decreased in the dorsal and median raphe (56 and 42%, respectively) and in the striatum (62%). Both 5-HTPacc and the ratio of the concentrations of 5-HIAA to 5-HT were decreased in the nucleus raphe magnus (46 and 27%, respectively), the dorsomedian medulla oblongata (52 and 51%), the locus coeruleus (62 and 40%) and the anterior hypothalamic nucleus (30 and 50%). In contrast, 5-HTPacc was increased in the ventrolateral medulla oblongata (55%) and the preoptic area (83%), but the 5-HIAA/5-HT ratio was lower in these two regions. Finally, 5-HIAA/5-HT ratio was also decreased in the periventricular nucleus and in the frontal cortex. Since various patterns of variations in 5-HTPacc and in 5-HIAA/5-HT ratio were observed, the factors affecting serotonin metabolism in hypoxic rats can be different among brain regions. These results show that, in the rat, long-term hypoxia induces changes in in vivo activity of tryptophan hydroxylase and in 5-HT and 5-HIAA content of some brain structures; some of these biochemical changes may be linked to adaptative mechanisms.
Poncet
L
L
Département de Médecine Expérimentale, INSERM U 52, CNRS ERS 5645, Université Claude Bernard, Lyon, France.
Denoroy
L
L
Dalmaz
Y
Y
Pequignot
J M
JM
D006916:5-Hydroxytryptophan / Q000378:metabolism; D000818:Animals; D065105:Aromatic Amino Acid Decarboxylase Inhibitors; D001921:Brain / Q000201:enzymology; D001923:Brain Chemistry / Q000187:drug effects / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006834:Hydrazines / Q000494:pharmacology; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D000860:Hypoxia / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D009411:Nerve Endings / Q000187:drug effects / Q000201:enzymology; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000378:metabolism* / Q000502:physiology; D014365:Tryptophan Hydroxylase / Q000378:metabolism*
D065105:Aromatic Amino Acid Decarboxylase Inhibitors; D004791:Enzyme Inhibitors; D006834:Hydrazines; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; C004297:3-hydroxybenzylhydrazine; D006916:5-Hydroxytryptophan; D014365:Tryptophan Hydroxylase