Red blood cells participate in the metabolic clearance of catecholamines in the rat.
The aim of the present study was to investigate the possible role of erythrocytes in the metabolic clearance of catecholamines (CAs) in the rat. Intravenous infusion of exogenous CAs (dopamine -DA-, norepinephrine -NE-, or epinephrine -Epi-) was carried out at increasing doses to cover a range of plasma concentrations from the lower to the upper physiological and to pharmacological levels. Whatever the mechanism(s) underlying the CAs erythrocyte/plasma balance: 1. it seemed more efficient at lower concentrations of CAs; 2. it reached an apparent plateau where plasma and erythrocyte concentrations were not statistically different; 3. finally, saturation was suggested when further increase in plasma concentration was associated with a lower response in erythrocytes. This series of experiments confirms previous reported results with human erythrocytes and suggests that rat erythrocytes could transport CAs from their sites of release to their sites of elimination. In a second series of experiments, the intra-erythrocyte metabolism of CAs was investigated. DA was strikingly increased in plasma and in erythrocytes 2 hours after 1,2-dimethyl-3-hydroxy-4-pyridone (CP20), 100 mg/kg i.p., known to inhibit catechol-O-methyl transferase. Our data demonstrate an increase in glucuro-conjugated DA in vivo (24 hours after CP20 injection) as well as in vitro (3 hours incubation at 37 degrees C), suggesting activation of the glucuroconjugating pathway. Increased glucuroconjugated DA after in vitro incubation demonstrates intra-erythrocyte synthesis while increased concentration in Ringer-Hepes medium demonstrates an inside-out transport of glucuro-conjugate. These data are the first evidence in favour of an intra-erythrocyte glucuro-conjugation of CAs in the rat.
Azoui
R
R
Department of Internal Medicine, Broussais H-D Faculty of Medicine, Paris, France.
Schneider
J
J
Dong
W X
WX
Dabiré
H
H
Safar
M
M
Cuche
J L
JL
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002395:Catecholamines / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics; D000077543:Deferiprone; D004298:Dopamine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000097:blood / Q000493:pharmacokinetics; D004837:Epinephrine / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D004912:Erythrocytes / Q000378:metabolism*; D006339:Heart Rate / Q000187:drug effects; D007262:Infusions, Intravenous; D008297:Male; D008657:Metabolic Clearance Rate; D009638:Norepinephrine / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D011728:Pyridones / Q000494:pharmacology; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar
D002395:Catecholamines; D011728:Pyridones; D000077543:Deferiprone; C037719:dopamine glucuronide; D004298:Dopamine; D009638:Norepinephrine; D004837:Epinephrine