Influence of clomipramine and embolization on the characterization of serotonin uptake in rabbit lung using a new mathematical model.
The kinetic parameters Vmax and Km of the carrier-mediated uptake of serotonin by the lung can be used as an index of endothelial distress. To this purpose we have recently developed a new mathematical model which estimates the kinetic parameters of the double uptake mechanism of serotonin by the rabbit lung (MODEL3, Peeters et al., 1989). The aim of the present study was to evaluate the behavior of this new model after inhibition of the uptake by clomipramine and after reduction of the perfused lung surface with glass bead embolization. Clomipramine administration did not cause distinct hemodynamic alterations, but decreased the serotonin extraction and Vmax/Km (the sum of all first order rate constants). After clomipramine, Vmax1, i.e., the maximal velocity for the first uptake pathway, was significantly decreased, while Km1 tended to increase without reaching significance. The virtual inhibition constant of clomipramine was about 1 microM. Glass bead embolization resulted in large hemodynamic responses, decreased extraction of serotonin and decreased values for Vmax/Km and Vmax1. This is consistent with a diminished vascular surface available for serotonin extraction. We conclude that MODEL3 was able to detect changes in intrinsic uptake capacity and vascular surface area, which were especially reflected in a decrease of Vmax/Km and Vmax1.
Peeters
F A
FA
Department of Medicine, University of Antwerp, Wilrijk, Belgium.
Bult
H
H
Herman
A G
AG
D000818:Animals; D002997:Clomipramine / Q000494:pharmacology*; D005260:Female; D007700:Kinetics; D008168:Lung / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008954:Models, Biological; D011655:Pulmonary Embolism / Q000378:metabolism*; D011817:Rabbits; D012701:Serotonin / Q000378:metabolism*
D012701:Serotonin; D002997:Clomipramine