Changes in sodium, potassium-ATPase induced by repeated fencamfamine: the roles of cyclic AMP-dependent protein kinase and the nitric oxide-cyclic GMP pathway.
Fencamfamine (FCF) is an indirect dopamine agent with effects similar to amphetamine and cocaine. In the present study, we investigate changes in Na,K-ATPase, cyclic AMP-dependent protein kinase (PKA) and nitric oxide synthase (NOS) activity and cyclic GMP levels in the nucleus accumbens (NAc) and striatum (ST) of animals acutely or repeatedly treated with FCF (3.5 mg/kg). Na,K-ATPase had a similar activity in control and repeatedly treated animals, but was reduced in the NAc of the acute group. This enzyme was reduced in the ST in acute and repeatedly treated animals, compared to the control group. Expression of the alpha(1,2,3)-Na,K-ATPase isoforms in the NAc and the ST was not altered in all groups studied. Acute FCF induced a significant increase in PKA activity in both the ST and the NAc. Repeatedly treated animals showed a higher increase in PKA activity in the NAc, but not in the ST, when compared to the acute group. There was also an increase in both NOS activity and cyclic GMP levels only in the NAc of FCF repeatedly treated animals compared to the acute and control groups. We suggest that chronic FCF treatment is linked to a modification in Na,K-ATPase activity through the PKA and NO-cyclic GMP pathway.
Munhoz
Carolina Demarchi
CD
Department of Pharmacology, Institute of Biomedical Sciences, University of Sao Paulo, Avenida Prof Lineu Prestes, 1524 Cidade Universitária, São Paulo 05508-900, SP, Brazil.
Glezer
Isaias
I
Kawamoto
Elisa Mitiko
EM
Araújo
Ana Paula Natalini
AP
Lepscha
Lucília B
LB
Planeta
Cleopatra S
CS
DeLucia
Roberto
R
Scavone
Cristoforo
C
D000818:Animals; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D006152:Cyclic GMP / Q000378:metabolism*; D004334:Drug Administration Schedule; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D009636:Norbornanes / Q000008:administration & dosage*; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*
D009636:Norbornanes; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D017868:Cyclic AMP-Dependent Protein Kinases; D000254:Sodium-Potassium-Exchanging ATPase; D006152:Cyclic GMP; C020900:fencamfamine