Environmental influences on uptake of serotonin and other amines

Abstract

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 0.25μM. The calculated fractional 5-HT clearance (fraction of 5-HT removed in single pass) was 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-5-HT 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 elevated p(O2) 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.