PMID- 9028636
OWN - NLM
STAT- MEDLINE
DCOM- 19970430
LR  - 20191210
IS  - 1064-1963 (Print)
IS  - 1064-1963 (Linking)
VI  - 19
IP  - 1-2
DP  - 1997 Jan-Feb
TI  - Short-term vs. sustained inhibition of proximal tubule Na,K-ATPase activity by 
      dopamine: cellular mechanisms.
PG  - 73-86
AB  - Dopamine (DA) produces a natriuresis attributed in part to inhibition of 
      Na,K-ATPase activity (NKA) in the proximal tubule (PCT), and impairment in this 
      inhibition has been linked to several forms of hypertension in animals. Here we 
      examined whether the intracellular signaling mechanisms involved are the same in 
      the early and late phases of this phenomenon. DA (1 microM) inhibited NKA 
      similarly after 15 min (by 38%) or 180 min (by 36%) incubation, taken to 
      represent short-term (ST) and sustained (Sd) pump regulation, respectively. 
      Calphostin C, a specific inhibitor of protein kinase C (PKC), completely blocked 
      the ST action of DA on NKA, whereas IP20, a specific inhibitor of protein kinase 
      (PKA), had no effect. In contrast, IP20 completely abolished the Sd (180 min) 
      inhibition by DA, whereas calphostin C had only a partial or variable effect. The 
      DA-1 agonist fenoldopam (which does not activate PKC but increases cAMP) alone 
      failed to inhibit the pump at 180 min (as it does also in the short-term in PCT), 
      suggesting that ST inhibition is required for the Sd effect to occur. 
      Furthermore, PTH1-34, a known ST inhibitor of NKA suppressed the pump at 180 min 
      (by 46%), but unlike in the short-term, this effect was completely prevented by 
      IP20. In contrast, PTH3-34, which does not stimulate adenylyl cyclase or activate 
      PKA, caused only a small (19%) and variable Sd inhibition. In conclusion, 
      short-term inhibition of the PCT pump by dopamine is mediated via PKC, whereas 
      the sustained inhibition requires the PKA pathway in addition to the ongoing 
      PKC-mediated effect.
FAU - Pinto-do-O, P C
AU  - Pinto-do-O PC
AD  - Department of Molecular Medicine, Karolinska Institute, Stockholm, Sweden.
FAU - Chibalin, A V
AU  - Chibalin AV
FAU - Katz, A I
AU  - Katz AI
FAU - Soares-da-Silva, P
AU  - Soares-da-Silva P
FAU - Bertorello, A M
AU  - Bertorello AM
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Clin Exp Hypertens
JT  - Clinical and experimental hypertension (New York, N.Y. : 1993)
JID - 9305929
RN  - 0 (Dopamine Agonists)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Naphthalenes)
RN  - E0399OZS9N (Cyclic AMP)
RN  - EC 2.7.11.13 (Protein Kinase C)
RN  - EC 7.2.2.13 (Sodium-Potassium-Exchanging ATPase)
RN  - I271P23G24 (calphostin C)
RN  - INU8H2KAWG (Fenoldopam)
RN  - VTD58H1Z2X (Dopamine)
SB  - IM
MH  - Animals
MH  - Cyclic AMP/agonists/metabolism
MH  - Dopamine/*pharmacology
MH  - Dopamine Agonists/pharmacology
MH  - Drug Interactions
MH  - Enzyme Inhibitors/pharmacology
MH  - Fenoldopam/pharmacology
MH  - Ion Transport/drug effects
MH  - Kidney Tubules, Proximal/cytology/drug effects/*enzymology
MH  - Male
MH  - Naphthalenes/pharmacology
MH  - Natriuresis/drug effects
MH  - Protein Kinase C/antagonists & inhibitors/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Signal Transduction/drug effects/*physiology
MH  - Sodium-Potassium-Exchanging ATPase/*antagonists & inhibitors/metabolism
EDAT- 1997/01/01 00:00
MHDA- 1997/01/01 00:01
CRDT- 1997/01/01 00:00
PHST- 1997/01/01 00:00 [pubmed]
PHST- 1997/01/01 00:01 [medline]
PHST- 1997/01/01 00:00 [entrez]
AID - 10.3109/10641969709080805 [doi]
PST - ppublish
SO  - Clin Exp Hypertens. 1997 Jan-Feb;19(1-2):73-86. doi: 10.3109/10641969709080805.