Environmental influences on uptake of serotonin and other amines.
Lungs accumulate 5-hydroxytryptamine (serotonin, 5-HT) from the perfusate by a sodium-dependent, energy-requiring, saturable process. The rate-limiting step for uptake is the transport of 5-HT and not its subsequent metabolism to 5-hydroxyindoleacetic acid. Autoradiographic studies indicate that the pulmonary endothelium is the cellular site of uptake. The effect of hyperoxia on lung clearance of 5-HT was studied with isolated perfused and ventilated lungs from rats that were previously exposed to hyperoxia. Lungs were perfused with recirculating electrolyte solution and initial [5-HT] of 0.24 microM. The calculated fractional 5-HT clearance (fracion of 5-HT removed in a single pass) ws 0.77 +/- 0.02 (mean +/- SE: n = 44) for control rats. Mean fractional clearance decreased by 20% in rats exposed to 1 atm O2 for 18 hr and 30% after 4 atmospheres absolute (ata) O2 for 1 hr (p < 0.05). The effects of O2 at 4 ata were in part reversed by exposure to air for 3.5 hr and in part prevented by injection of superoxide dismutase (60 nmole/kg body weight). This degree of O2 exposure at either 1 or 4 ata had no effect on lung content of adenine nucleotides or the distribution of 3H-5HT on autoradiography. Rats maintained for 6 weeks on a vitamin E-deficient diet showed an increased effect of hyperoxia on 5-HT clearance and did not show reversal of changes after 24 hr of air breathing. The results indicate that exposure to elevatd po2 results in reversible depression of pulmonary 5-HT clearance that is potentiated by vitamin E deficiency. This suggests alteration of pulmonary endothelial membrane transport properties due to O2 toxicity.
D000588:Amines / Q000378:metabolism*; D000818:Animals; D001273:Atmosphere Exposure Chambers; D001693:Biological Transport, Active; D006931:Hyperbaric Oxygenation; D007099:Imipramine / Q000378:metabolism; D008168:Lung / Q000378:metabolism* / Q000648:ultrastructure; D009638:Norepinephrine / Q000378:metabolism; D010100:Oxygen / Q000506:poisoning*; D010477:Perfusion; D051381:Rats; D012701:Serotonin / Q000378:metabolism*; D014811:Vitamin E Deficiency / Q000378:metabolism
D000588:Amines; D012701:Serotonin; D007099:Imipramine; D010100:Oxygen; D009638:Norepinephrine