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 e rythrocytes in the metabolic clearance of catecholamines (CAs) in the rat. Intravenous infusion of exogenous CAs (dopamine -DA-, norepinephr ine -NE-, or epinephrine -Epi-) was carried out at increasing doses to cover a range of plasma concentrations from the lower to the upper ph ysiological and to pharmacological levels. Whatever the mechanism(s) u nderlying the CAs erythrocyte / plasma balance: 1. it seemed more effi cient at lower concentrations of CAs; 2. it reached an apparent platea u where plasma and erythrocyte concentrations were not statistically d ifferent; 3. finally, saturation was suggested when further increase i n plasma concentration was associated with a lower response in erythro cytes. This series of experiments confirms previous reported results w ith human erythrocytes and suggests that rat erythrocytes could transp ort CAs from their sites of release to their sites of elimination. In a second series of experiments, the intra-erythrocyte metabolism of CA s was investigated. DA was strikingly increased in plasma and in eryth rocytes 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 dem onstrate 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 glucuro-conjugated DA after in vitro incubation demonstrates intra-er ythrocyte synthesis while increased concentration in Ringer-Hepes medi um demonstrates an inside-out transport of glucuro-conjugate. These da ta are the first evidence in favour of an intra-erythrocyte glucuro-co njugation of CAs in the rat.