Single-pass removal of [14C]-5-hydroxytryptamine and [3H]norepinephrine by rabbit lung, in vivo: kinetics and sites of removal

Abstract

Multiple indicator dilution techniques were employed to study the kinetics and sites of removal of [14C]-5-hydroxytryptamine (5-HT) and [3H]norepinephrine (NE) by rabbit lung in vivo. Percentage of single-pass transpulmonary removal of 5-HT decreased from 87 +/- 2 to 73 +/- 3, 49 +/- 7 and 34 +/- 2% when the total dose of administered 5-HT was increased from 8 X 10(-9) to 30, 75 and 150 X 10(-9) mol, respectively. Similarly, percentage of removal of NE decreased from 23 +/- 2 to 18 +/- 2, 1 +/- 2 and 5 +/- 2% when the amount of NE administered was increased from 0.3 X 10(-9) to 10, 50 and 100 X 10(-9) mol, respectively. From these data, kinetic constants of removal were calculated assuming either homogeneous or heterogeneous pulmonary perfusion; values for the apparent Michaelis-Menten constant (Km) averaged 1.1 +/- 0.4 X 10(-6) M (5-HT) and 0.9 +/- 0.3 X 10(-6) M (NE), whereas values for the apparent maximal velocity of removal (Vmax) were 17.4 +/- 2.6 X 10(-9) mol/min/g of lung wet weight (5-Ht) and 4.0 +/- 0.9 X 10(-9) mol/min/g of lung wet weight (NE). Furthermore, increasing the dose of administered 5-HT had little effect on NE removal and, similarly, increasing the dose of NE caused only small reductions in 5-HT extraction, indicating distinct sites of removal of these two amines by rabbit pulmonary endothelium.