Serotonin uptake and metabolism in isolated, perfused fetal, newborn and adult rabbit lungs

Abstract

Twenty-second infusions of³H-5HT were made into the pulmonary arteries of lungs isolated at three different stages of rabbit development: 1) nonventilated lungs from previable 26- to 27-d fetuses; 2) ventilated, newborn lungs from rabbits within 12 hours of birth; and 3) ventilated, young adult lungs. The concentration of 5HT infused (0.65 to 1.12×10⁻⁸ M) was much less than the apparent Km for the 5HT uptake process. At these low concentrations 5HT infusion produced no observable vasoactivity. In order to assure a constant ratio of flow to capillary surface area (independant of lung size), perfusate flow was adjusted to produce an approximately 7-second dye retention time. Under these conditions fetal and adult lungs allow 45–50% of³H-5HT to pass through unmetabolized, but newborn lungs allow only about 15% of the unmetabolized³H-5HT through. As previously demonstrated by other workers, essentially no³H-5HT metabolites appeared in the effluent of adult lungs. In contrast about 20 percent of the radioactivity recovered from the immature lungs was eluted with the dye peak as metabolites of³H-5HT. 10⁻⁴ M imipramine added to the perfusate blocked 5HT uptake and metabolism similarly at all three stages of development. Therefore, uptake does not seem to be by passive diffusion in immature lungs. The presence of avid 5HT inactivation in previable, fetal lungs with peak inactivation observed in newborn lungs may correlate with the prominence and functional importance of 5HT within pulmonary neuroendocrine cells during perinatal life.