Tracer microinjection studies of prostaglandin E-2 transport in the rat nephron

Abstract

Urinary excretion and tubular handling of 3-H-prostaglandin E2 (3-H-PGE2) were examined in anesthetized rats made diuretic with 2.5% saline infusion using the tracer microinjection technique. Radioactive inulin and PGE2 were simultaneously injected into surface convolutions of proximal and distal tubules with volumetric micropipettes and their urinary excretion were measured. The rate of microinjection was adjusted to approximate tubular flow. Net 3-H-PGE2 recoveries from the microinjected kidney were similar following injections into early (61.2 plus or minus 6.8%) and late (62.9 plus or minus 7.9%) proximal tubules, but significantly higher after injection into distal tubules (91.3 plus or minus 7.0%) indicating absorption of 3-H-PGE2 in the loop of Henle but not in the proximal and distal nephron. Excretion was primarily direct, that is, parallel with inulin excretion when PGE2 was deposited in distal convoluted tubules. After injection of 3-H-PGE2 into early and late proximal tubules, half of net recovery was direct and half showed temporal dissociation from inulin (indirect recovery), revealing retardation of PGE2 excretion in the loop. Segmental tubular efflux occurred primarily in the loop of Henle (48.5%). It was low in the distal nephron (13.5%) and negligible in the proximal convoluted tubule (6.1%). These studies indicate that the loop of Henle is the principal site of transtubular PGE2 movement. They do not suggest a primary tubular route of transfer of medullary prostaglandins to cortical vascular or peritubular sites of action except for possible inhibition of distal reabsorption from the luminal side.