Effects of (Sp)- and (Rp)-adenosine cyclic 3',5'-phosphorothioates on electrolyte excretion by the isolated perfused rat kidney.
We studied the effects of the (Sp) and (Rp) diastereomers of the phosphorothioate analogue of cyclic AMP (cAMPS) on the excretion of electrolytes in the isolated perfused rat kidney. cAMPS is highly permeant across the peritubular cell membrane and is not metabolized by the rat kidney (Coulson et al., Life Sci. 32: 1489-1498, 1983). Addition of 10 microM cAMPS(Sp) to the perfusate resulted in a significant phosphaturia, bicarbonaturia, magnesuria and natriuresis and no change in renal vascular resistance or glomerular filtration rate. Fractional excretion of calcium was elevated by cAMPS(Sp) but proportionately less than the fractional excretion of sodium so that the ratio of calcium to sodium clearances was significantly lowered. cAMPS(Rp) 10 or 100 microM was without effect on renal electrolyte excretion. The parathyroid hormone-like effects of the (Sp) diastereomer are consistent with its known ability to activate protein kinase.
Scheinman
S J
SJ
Stec
W J
WJ
Coulson
R
R
D000818:Animals; D000242:Cyclic AMP / Q000031:analogs & derivatives* / Q000494:pharmacology; D004573:Electrolytes / Q000652:urine*; D005919:Glomerular Filtration Rate / Q000187:drug effects; D066298:In Vitro Techniques; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D010477:Perfusion; D051381:Rats; D011919:Rats, Inbred Strains; D013237:Stereoisomerism; D013873:Thionucleotides / Q000494:pharmacology*; D014655:Vascular Resistance / Q000187:drug effects
D004573:Electrolytes; D013873:Thionucleotides; C016957:adenosine-3',5'-cyclic phosphorothioate; D000242:Cyclic AMP