P1,P4-diadenosine tetraphosphate (Ap4A) inhibits proximal tubular reabsorption of sodium in rats.
OBJECTIVE
P1,P4-diadenosine tetraphosphate (Ap4A) is a vasoactive dinucleotide possessing natriuretic activity. It is unclear, however, which part of the nephron is the target site of action for Ap4A.


METHODS
We evaluated the tubular sites of Ap4A action using the lithium clearance technique.


RESULTS
Ap4A at a priming dose of 2 micromol/kg with subsequent infusion at 20 nmol/kg/min increased fractional water and sodium excretion 2.5- and 5.6-fold, respectively. Moreover, Ap4A increased lithium clearance 1.9-fold and fractional lithium excretion 2.8-fold. Fractional water and sodium excretion from distal nephron segments was not significantly affected by Ap4A.


CONCLUSIONS
These results suggest that Ap4A induces natriuresis mainly through inhibition of proximal tubular reabsorption of sodium.
Stiepanow-Trzeciak
Anna
A
Department of Monitoring Therapy and Pharmacogenetics, Medical University of Gdansk, Gdansk, Poland.
Jankowski
Maciej
M
Angielski
Stefan
S
Szczepanska-Konkel
Miroslawa
M
D000327:Adsorption; D000818:Animals; D015226:Dinucleoside Phosphates / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000378:metabolism*; D008094:Lithium / Q000378:metabolism*; D008297:Male; D008657:Metabolic Clearance Rate / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D012964:Sodium / Q000378:metabolism*
D015226:Dinucleoside Phosphates; C020733:diadenosine tetraphosphate; D008094:Lithium; D012964:Sodium