Cyclosporine A and purinergic receptors in rat kidney.
Previous reports have demonstrated that Cyclosporine A (CyA) chronically administered induces an increase in adenosine plasma concentration by inhibiting adenosine uptake by red blood cells (RBC). We hypothesized that this effect may modulate, by a down regulation, the mRNA expression of adenosine receptors in rat kidney. Since high blood pressure (HBP) is a classical side effect of CyA treatment, nicardipine, a dihydropyridine calcium channel blocker, is often associated with CyA in treatment. To distinguish between the effects of CyA-induced HBP and the effects of CyA by itself, we have evaluated the effects of CyA and/or nicardipine on the mRNA expression of A1 and A2a adenosine receptors. The study was performed on five groups of rats (n= 8) receiving during 21 days either serum saline (0.5 ml i.p), CyA (12 mg/kg/day, i.p), nicardipine (1.2 mg/kg i.p) or nicardipine + CyA. The last (or fifth) group was injected with vehicle (0.5 ml i.p). Blood samples for adenosine assay were collected in the renal artery at day 21, just before the rat kidneys were removed for quantitation of adenosine A1 and A2a mRNA concentration by RT-PCR. We make two conclusions :i) Nicardipine induces a decrease in mRNA expression of A1 but not of A2a adenosine receptors. However, because nicardipine lowered both blood pressure and A1 mRNA expression, it is not possible to conclude if A1 mRNA decrease is implicated in the nicardipine effects on blood pressure.ii) CyA induces an increase in renal artery adenosine concentration and a decrease in mRNA expression of A1 and A2a adenosine receptors.
Halimi
G
G
UMR CNRS 6560 Laboratoire de Biochimie et d'Ingenierie des Protéines, Faculté de Médecine Secteur Nord, Marseille, France.
Sampol
J
J
Clot-Faybesse
O
O
Mercier
L
L
Devaux
C
C
Berland
Y
Y
Dussol
B
B
Rochat
H
H
Guieu
R
R
D000241:Adenosine / Q000097:blood*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology; D016572:Cyclosporine / Q000097:blood / Q000494:pharmacology* / Q000633:toxicity; D005260:Female; D007166:Immunosuppressive Agents / Q000097:blood / Q000494:pharmacology* / Q000633:toxicity; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism*; D009529:Nicardipine / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018047:Receptors, Purinergic P1 / Q000096:biosynthesis*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D002121:Calcium Channel Blockers; D007166:Immunosuppressive Agents; D012333:RNA, Messenger; D018047:Receptors, Purinergic P1; D016572:Cyclosporine; D009529:Nicardipine; D000241:Adenosine