Depression of pulmonary 5-hydroxytryptamine uptake by metabolic inhibitors.
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.
D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D002250:Carbon Radioisotopes; D002746:Chlorpromazine / Q000494:pharmacology; D002855:Chromatography, Thin Layer; D003486:Cyanides / Q000494:pharmacology; D003847:Deoxyglucose / Q000494:pharmacology; D003864:Depression, Chemical; D006168:Guinea Pigs; D000860:Hypoxia / Q000378:metabolism; D007099:Imipramine / Q000494:pharmacology; D066298:In Vitro Techniques; D007461:Iodoacetates / Q000494:pharmacology; D007490:Iproniazid / Q000494:pharmacology; D008168:Lung / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D010042:Ouabain / Q000494:pharmacology; D010477:Perfusion; D012701:Serotonin / Q000378:metabolism*; D013997:Time Factors
D002250:Carbon Radioisotopes; D003486:Cyanides; D007461:Iodoacetates; D012701:Serotonin; D010042:Ouabain; D003847:Deoxyglucose; D007490:Iproniazid; D007099:Imipramine; D002746:Chlorpromazine