The effects of folic acid administration on the weight, protein, water content and microsomal 5'-phosphodiesterase of the rat kidney were determined, to elucidate the mechanisms contributing to the renal enlargement produced by this agent. Folic acid administered ip in single doses of 100-250 mg/kg caused dose-related increases in kidney weight, water and protein content within 24 hr. Time-course studies indicated that 250 mg folic acid/kg given ip produced a progressive elevation in renal water content from 2 to 72 hr. Smaller increases in whole-kidney protein were recorded 8, 24 and 72 hr after folic acid treatment. However, a biphasic response of microsomal 5'-phosphodiesterase was produced, inhibition at 16 hr being followed by stimulation (to 140% of control) at 72 hr. In vitro studies indicated that folic acid inhibits 5'-phosphodiesterase competitively, and the early inhibition of 5'-phosphodiesterase in vivo appears to be due to a direct effect of folic acid on the enzyme.
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