INHIBITION OF INVITRO CONCENTRATIVE PROSTAGLANDIN ACCUMULATION BY PROSTAGLANDINS, PROSTAGLANDIN ANALOGS AND BY SOME INHIBITORS OF ORGANIC ANION TRANSPORT

Incubation of rabbit choroid plexus, anterior uvea (iris-ciliary body complex) or slices of kidney cortex in a medium containing 3H-labeled prostaglandin F2.alpha. ([3H]PGF2.alpha.) or E1 ([3H]PGE1) results in a 4- to 13- fold concentrative accumulation of 3H activity. Addition of PGF2.alpha., PGE1 or PGA1, any 1 of 5 PG analogues or a PG precursor, arachidonic acid, at a concentration of 10-4 M reduced the active accumulation of [3H]PGs by 47-97%. Octanoic acid, at the same concentration, had only a moderate effect on the choroid plexus and no significant inhibitory effect on [3H]PGF2.alpha., accumulation by anterior urea or kidney cortex. Inhibition was obtained with 2 mM iodoacetate (under anaerobic conditions) and with 10-4 M diphloretin phosphate, probenecid, iodipamide, indomethacin or dinitrophenol. Perchlorate (10-4 M) and I- (10-4 or 10-3 M) had no inhibitory effect, while 10-4 M p-aminohippuric acid had a significant inhibitory effect on the kidney cortex at a concentration of 10-4 M and on the anterior uvea at 10-3 M. The apparent carrier mediated PG transport systems of the choroid plexus, anterior uvea and kidney cortex are not related to the I- transport system, but may represent a subcomponent of the iodipamide transport system of these tissues. The systemic distribution and the rate of renal excretion of PGs probably could be altered by high concentrations of PGs, pharmacologically less active PG analogues, some inhibitors of organic acid transport and by some inhibitors of PG synthesis and PG action.