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Titolo:
1,1'-DIISOPROPYL-2,4'-CYANINE (DISPROCYNIUM24), A POTENT UPTAKE(2) BLOCKER, INHIBITS THE RENAL EXCRETION OF CATECHOLAMINES
Autore:
GRAEFE KH; FRIEDGEN B; WOLFEL R; BOSSLE F; RUSS H; SCHOMIG E;
Indirizzi:
UNIV WURZBURG,DEPT PHARMACOL & TOXICOL,VERSBACHER STR 9 D-97078 WURZBURG GERMANY UNIV REGENSBURG,DEPT NEUROL D-93043 REGENSBURG GERMANY UNIV HEIDELBERG,DEPT PHARMACOL D-69120 HEIDELBERG GERMANY
Titolo Testata:
Naunyn-Schmiedeberg's archives of pharmacology
fascicolo: 1, volume: 356, anno: 1997,
pagine: 115 - 125
SICI:
0028-1298(1997)356:1<115:1(APUB>2.0.ZU;2-9
Fonte:
ISI
Lingua:
ENG
Soggetto:
EXTRANEURONAL NORADRENALINE TRANSPORT; RAT KIDNEYS; TUBULAR SECRETION; URINARY-EXCRETION; ORGANIC CATIONS; DOPAMINE; NOREPINEPHRINE; METABOLISM; EPINEPHRINE; RABBIT;
Keywords:
DISPROCYNIUM24; NORADRENALINE; ADRENALINE; DOPAMINE; RENAL EXCRETION; ORGANIC CATION TRANSPORT; INULIN CLEARANCE; UPTAKE(2);
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
40
Recensione:
Indirizzi per estratti:
Citazione:
K.H. Graefe et al., "1,1'-DIISOPROPYL-2,4'-CYANINE (DISPROCYNIUM24), A POTENT UPTAKE(2) BLOCKER, INHIBITS THE RENAL EXCRETION OF CATECHOLAMINES", Naunyn-Schmiedeberg's archives of pharmacology, 356(1), 1997, pp. 115-125

Abstract

1,1'-Diisopropyl-2,4'-cyanine (disprocynium24), a potent inhibitor ofthe extraneuronal monoamine transport system (uptake(2)), was previously shown to reduce the clearance of catecholamines from plasma not only by blocking uptake, but presumably also by blocking organic cation transport. To provide more direct evidence for the latter conclusion, the present study was carried out in anaesthetized rabbits. It aimed at determining the effect of disprocynium24 on the renal excretion of catecholamines which is known to be, at least in part, a consequence oforganic cation transport in the kidney. To this end, the plasma clearance 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 disprocynium24 (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 II (monoamine oxidase and catechol-O-methyltransferase inhibited). A third group of animals with intact monoamine oxidase and catechol-O-methyltransferase was used to study the effect of disprocynium24 on the glomerular filtration rate (as determined by measuring the plasma clearance of inulin). In vehicle controls, Cl-u of endogenous adrenaline, noradrenaline and dopamine was 7.2, 5.2 and 153.6 ml kg(-1) min(-1), respectively, in group I and 10.4, 7.0 and 134.3 ml kg(-1) min(-1), respectively, 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 and15.4 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 inurine (i.e., 98% in group I and 92% in group II) was derived from thekidneys rather than from the circulation. By contrast, only about onequarter 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 bothgroups, disprocynium24 markedly reduced the Cl-u of endogenous catecholamines (by 72-90%) and of infused H-3-catecholamines (by 49-69%). Moreover, it preferentially inhibited the renal excretion of those components of urinary dopamine and noradrenaline which were derived from the kidney. Therefore, disprocynium24 inhibits the tubular secretion of catecholamines and, hence, organic cation transport in the kidney. This conclusion was substantiated by the observation that disprocynium24 did not alter the glomerular filtration rate.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 08/07/20 alle ore 07:58:15