Abstract

Since it is replete with degradative enzymes, the liver is commonly viewed as the organ primarily responsible for clearing circulating substances which are eliminated by metabolism. However, the enzyme content of an organ is not the only determinant of clearance. The relative tissue perfusion, a determinant of substrate delivery, is also an important factor. On the basis of enzyme content, clearance of 5-hydroxytryptamine (5-HT) by rat liver would be predicted to be greater than that by rat lung, since liver contains more than 10 times as much monoamine oxidase. However, pulmonary blood flow and, hence, substrate delivery is greater than that of liver. To examine the effect of tissue perfusion, the clearance of [14C]5-HT was studied in isolated, perfused rat lung and liver at several flows. The clearance of 5-HT was found to increase, while the extraction ratio decreased, with increasing flow in both organs. At normal (i.e., in vivo) organ flows, hepatic 5-HT clearance was only one-third of that observed in lung. The pulmonary 5-HT extraction ratio was greater than 0.90 at low flows, but was only 0.43 at normal flow. Attempts to predict the clearance of 5-HT from monoamine oxidase enzyme kinetic parameters determined in organ homogenates were successful for liver, but underestimated the observed pulmonary clearance. These results suggest that, despite its relative deficiency in degradative enzyme, the rat lung plays a major role in the total body clearance of circulating 5-HT.