Enflurane, halothane, and isoflurane inhibit removal of 5-hydroxytryptamine from the pulmonary circulation

We were interested in determining the effect of enflurane, halothane, and isoflurane on the uptake and removal of 5-hydroxytryptamine (5-HT) and phenylethylamine (PEA) from the lung. Isolated rabbit lungs were perfused in a recirculating system in vitro with 0.1 microM [14C]5-HT or 0.1 microM [14C]PEA in Krebs-Ringer solution. The rate of removal and percentage of removal of the bioamines were determined before and after either 1, 2, or 4 MAC multiples of the potent anesthetics. Because of variation in removal of bioamines among lungs from different animals, the effects of anesthetics on bioamine removal were determined by calculating the percentage of inhibition of removal using data from the control and test period for each lung. At 2 MAC concentrations, the anesthetics inhibited 5-HT removal 11.1%, at 4 MAC concentrations the anesthetics inhibited 5-HT removal 29.8% and significantly prolonged the half-life (t 1/2) of 5-HT removal. There was significant (10.8%) inhibition of PEA removal at 4 MAC concentrations for the three anesthetics. As uptake of 5-HT is the rate-limiting step in 5-HT removal, these data demonstrate a uniform depression of 5-HT uptake by the three potent anesthetics. The rate-limiting step of PEA uptake, metabolism by monoamine oxidases, is inhibited at 4 MAC concentrations of anesthetics.