The effects of probenecid on cyclic adenosine 3',5'-monophosphate levels in cerebrospinal fluid and on brain phosphodiesterase activity in the rat.
In rats, probenecid exhibits a dose-dependent increase in the concentration of cyclic adenosine 3',5'-monophosphate (cAMP) in cisternal cerebrospinal fluid (CSF). Maximal accumulation is reached 2 h after IP administration at a dosage of 150 mg/kg body weight. Serum levels of cAMP are unchanged after 200 mg/kg probenecid. In vitro investigations show an inhibitory effect of probenecid on the uptake of cAMP into the isolated choroid plexus of the rabbit. A non-competitive inhibition of probenecid on a high affinity fraction of cyclic nucleotide phosphodiesterase from rat brain homogenates is demonstrated with an inhibitor constant of 3.4 X 10(-3M. The results appear to validate the "probenecid test" for cAMP in clinical diagnostics.
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000201:enzymology; D002831:Choroid Plexus / Q000187:drug effects; D003563:Cyclic CMP / Q000134:cerebrospinal fluid*; D003597:Cytosine Nucleotides / Q000134:cerebrospinal fluid*; D004305:Dose-Response Relationship, Drug; D007700:Kinetics; D008297:Male; D009115:Muridae; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism*; D011339:Probenecid / Q000494:pharmacology*
D003597:Cytosine Nucleotides; D003563:Cyclic CMP; D010727:Phosphoric Diester Hydrolases; D011339:Probenecid