Depression of pulmonary 5-hydroxytryptamine uptake by metabolic inhibitors

Abstract

Energy requirements for uptake of 14-C labeled 5-hydroxytryptamine ([14-C]5-HT) were studied in isolated guinea pig lungs, ventilated with 95% O2-5% CO2 and perfused in a recirculating system with Krebs-Ringer-bicarbonate solution containing 4% bovine serum albumin and 5 mM glucose. After 14 min preincubation with various inhibitors, lungs were perfused for 30 min with 0.25 times 10- minus 6 M [14-C]5-HT. Aliquots of perfusate were analyzed for [14-C]5-HT and metabolic products. Control lungs had a fractional serotonin clearance of 0.57 plus or minus 0.04. The rate of removal of [14-C]5-HT was inhibited 96% by imipramine, 88% by chlorpromazine, and 65% by ouabain, but was unaffected by iproniazid. Anoxia and cyanide each inhibited uptake by 68%. Omitting glucose from the perfusate reduced uptake by 30%. 2-Deoxyglucose and iodoacetate decreased the rate of [14-C]5-HT removal by 44 and 70%, respectively. Uptake was not affected by lung weight gain nor by changes in lung mechanical properties produced by [14-C]5-HT. [14-C]5-HT uptake by guinea pig lung requires a metabolic source of energy providing additional evidence for transport by an active process.