1,1'-DIISOPROPYL-2,4'-CYANINE (DISPROCYNIUM24), A POTENT UPTAKE(2) BLOCKER, INHIBITS THE RENAL EXCRETION OF CATECHOLAMINES

1,1'-Diisopropyl-2,4'-cyanine (disprocynium24), a potent inhibitor of the extraneuronal monoamine transport system (uptake(2)), was previous ly shown to reduce the clearance of catecholamines from plasma not onl y by blocking uptake, but presumably also by blocking organic cation t ransport. To provide more direct evidence for the latter conclusion, t he present study was carried out in anaesthetized rabbits. It aimed at determining the effect of disprocynium24 on the renal excretion of ca techolamines which is known to be, at least in part, a consequence of organic cation transport in the kidney. To this end, the plasma cleara nce due to renal excretion (Cl-u) of endogenous as well as infused H-3 -labelled adrenaline, noradrenaline and dopamine was determined for 60 -min periods of urine collection in rabbits treated either with dispro cynium24 (270 nmol kg(-1) i.v followed by i.v. infusion of 80 nmol kg( -1) min(-1)) or vehicle. Two groups of animals were studied: group I ( monoamine oxidase and catechol-O-methyltransferase intact) and group I I (monoamine oxidase and catechol-O-methyltransferase inhibited). A th ird group of animals with intact monoamine oxidase and catechol-O-meth yltransferase was used to study the effect of disprocynium24 on the gl omerular filtration rate (as determined by measuring the plasma cleara nce of inulin). In vehicle controls, Cl-u of endogenous adrenaline, no radrenaline and dopamine was 7.2, 5.2 and 153.6 ml kg(-1) min(-1), res pectively, in group I and 10.4, 7.0 and 134.3 ml kg(-1) min(-1), respe ctively, in group II. Similar control values of Cl-u were obtained for infused H-3-adrenaline and H-3-noradrenaline, but not for infused H-3 -dopamine; Cl-u of H-3-dopamine (4.9 ml kg(-1) min(-1) in group I and 15.4 ml kg(-1) min(-1)min-1 in group II) was considerably smaller than Cl-u of endogenous dopamine, indicating that most of the dopamine in urine (i.e., 98% in group I and 92% in group II) was derived from the kidneys rather than from the circulation. By contrast, only about one quarter of the noradrenaline in urine (32% in group I and 24% in group II) and none of the urinary adrenaline were of renal origin. In both groups, disprocynium24 markedly reduced the Cl-u of endogenous catecho lamines (by 72-90%) and of infused H-3-catecholamines (by 49-69%). Mor eover, it preferentially inhibited the renal excretion of those compon ents of urinary dopamine and noradrenaline which were derived from the kidney. Therefore, disprocynium24 inhibits the tubular secretion of c atecholamines and, hence, organic cation transport in the kidney. This conclusion was substantiated by the observation that disprocynium24 d id not alter the glomerular filtration rate.