Pharmacodynamic analysis of substrate stimulation of p-aminohippurate transport by newborn rabbit kidney

Abstract

Penicillin pretreatment of 2-week-old New Zealand White rabbits significantly increased the ability of renal cortical slices to transport p-aminohippuric acid (PAH). The PAH slice/medium ratio increased with dose to a maximum at 90,000 I.U. of procaine penicillin G. Sodium penicillin G (180,000 I.U.) produced no greater increase. Stimulation was maximal after four penicillin injections at 12-hour intervals. The maximal response was observed 24 hours after the final injection, whereas after 72 hours the capacity of slices from treated animals to transport PAH was no different than control. To determine the effect of a maximal substrate challenge on the development of transport capacity, pregnant does were treated with 90,000 I.U. of procaine penicillin i.m. twice daily through the last half of gestation. Young animals received four penicillin injections before sacrifice. The PAH slice/medium ratio from pups 3 days, 1 and 2 weeks old were not significantly different from that normally observed at 4 weeks. Animals 4 weeks old did not respond to penicillin treatment. Thus, intrinsic transport capacity for PAH is mature at 4 weeks of age. Only before this age may transport be enhanced by substrate. Maximal enhancement of PAH transport capacity occurs when four injections of 90,000 I.U. of procaine penicillin G are administered at 12-hour intervals followed by sacrifice 24 hours after the final injection.