Short-term regulation of Na+,K(+)-ATPase activity by dopamine.
The short term regulation of the activity of the Na,K-pump (Na+,K(+)-ATPase) is just beginning to be understood. By using single microdissected proximal tubule segments (PCT) (permeabilized in order to clamp Na entry), it was possible to study regulation of Na+,K(+)-ATPase activity in its own environment and in a well defined cell population. The Na+,K(+)-ATPase activity can be regulated over a short term via guanidine triphosphate (GTP) dependent regulatory proteins. However the guanidine proteins are not directly coupled to the Na,K-pump and the mechanism involves the activation of complex intracellular signalling system. Locally produced dopamine induces a dose dependent inhibition of Na+,K+ ATPase activity. This inhibition is mediated by a complex mechanism that requires the activation of both membrane dopamine receptors, DA-1 and DA-2. It involves the activation of a pertussis toxin sensitive GTP-binding protein and activation of protein kinase C. A DA-2 agonist only inhibits Na+,K(+)-ATPase activity when it is incubated together with dibutyryl cAMP or Forskolin. We have therefore concluded that an increase in cellular cAMP levels plays a permissive role for DA-2 inhibition of Na+,K(+)-ATPase activity. A fully differentiated cell is required for dopamine inhibition of Na+,K(+)-ATPase activity. An abnormal regulation of proximal tubule Na+,K(+)-ATPase activity might be of importance in the pathogenesis of certain types of hypertension.
Bertorello
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Department of Pediatrics, St. Göran's Children's Hospital, Karolinska Institute, Stockholm, Sweden.
Aperia
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D000818:Animals; D000831:Animals, Newborn; D004298:Dopamine / Q000494:pharmacology*; D006801:Humans; D006973:Hypertension / Q000201:enzymology; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013997:Time Factors
D000254:Sodium-Potassium-Exchanging ATPase; D004298:Dopamine