Dopaminergic modulation of Na,K-ATPase activity in the proximal tubules of normotensive and hypertensive rats.
Renal proximal tubular Na,K-ATPase plays an important role in the maintenance of sodium homeostasis and it is known that dopamine (DA) exerts an inhibitory effect on the activity of this enzyme. We have found that DA-induced inhibition of Na,K-ATPase is abolished in the spontaneously hypertensive rats (SHR) in comparison with age-matched Wistar-Kyoto (WKY) rats. Dopamine inhibits Na,K-ATPase via phospholipase C coupled protein kinase C pathway. The enzyme protein kinase C subsequently causes inhibition of Na,K-ATPase. In the SHR, DA-induced activation of phospholipase C is diminished, which in turn is responsible for the abolished inhibition of Na,K-ATPase. We have now shown that DA-induced activation of protein kinase C, which results from activation of DA-1 receptors is also abolished in the SHR which would account for the failure of DA to inhibit Na,K-ATPase in the hypertensive animals. Recently, we have examined the possibility that the failure of DA to inhibit Na,K-ATPase activity may be related to abnormal expression of DA receptors. In radioligand binding studies with [3H] SCH 23390 as a DA-1 receptor ligand and [3H] spiroperidol as a DA-2 receptor ligand we showed that both [3H] SCH 23390 and [3H] spiroperidol bindings are best fit to one site model in either WKY or SHR. Both Bmax and KD of either ligand binding to proximal tubule in the SHR were not statistically different from their WKY counterparts.(ABSTRACT TRUNCATED AT 250 WORDS)
Lokhandwala
M F
MF
College of Pharmacy, University of Houston, TX 77204-5511, USA.
Kansra
V
V
Chen
C
C
D000818:Animals; D004298:Dopamine / Q000502:physiology*; D006973:Hypertension / Q000201:enzymology* / Q000235:genetics; D007687:Kidney Tubules, Proximal / Q000201:enzymology* / Q000502:physiology*; D007700:Kinetics; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D011954:Receptors, Dopamine / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors / Q000502:physiology*
D011954:Receptors, Dopamine; D000254:Sodium-Potassium-Exchanging ATPase; D004298:Dopamine