Mechanism of renal tubular secretion of norepinephrine in the rabbit.
The present studies examined renal tubular secretory mechanisms for norepinephrine (NE) in the anesthetized rabbit. The application of a saline droplet containing [3H]NE and [14C]inulin to the decapsulated surface of the left kidney was associated with a greater urinary recovery of 3H from that kidney than from the right kidney. The urinary ratio of 3H to 14C was greater than that in the droplet [ratio of urinary 3H/14C to droplet 3H/14C (U/D) = 8.6 +/- 1.2, P < .005], indicating tubular influx of [3H]NE. The urinary recoveries of [14C]inulin from both kidneys were not significantly different from each other. At peak excretion, nonmetabolized [3H]NE represented 74 +/- 8% of the 3H excreted from the left kidney. Probenecid significantly suppressed, but did not abolish, the tubular influx of 3H, but did not significantly alter the fraction of total 3H excreted as nonmetabolized [3H]NE. Cyanine 863 virtually abolished the tubular influx of 3H and significantly reduced the fraction of total 3H excreted as nonmetabolized [3H]NE. Surface application of [3H]-p-aminohippurate or [14C]tetraethylammonium produced U/D ratios which were indicative of tubular influx of the ions. Probenecid abolished the tubular influx of [3H]-p-aminohippurate (P < .001), whereas cyanine 863 significantly reduced the tubular influx of [14C]tetraethylammonium (P < .001). Surface application of [3H]mannitol resulted in no evidence of tubular influx (U/D = 1.2 +/- 0.3, N.S.). The results demonstrate that 1) [3H]NE was secreted by the rabbit renal tubule; 2) passive diffusion probably accounted for little of the tubular influx of [3H]NE; and 3) three-quarters of the secreted [3H]NE was secreted as nonmetabolized NE, most likely via cationic transport.
D000818:Animals; D002250:Carbon Radioisotopes; D007684:Kidney Tubules / Q000378:metabolism*; D008297:Male; D009638:Norepinephrine / Q000378:metabolism*; D011339:Probenecid / Q000494:pharmacology; D011817:Rabbits; D013757:Tetraethylammonium Compounds / Q000378:metabolism; D014316:Tritium; D010130:p-Aminohippuric Acid / Q000378:metabolism
D002250:Carbon Radioisotopes; D013757:Tetraethylammonium Compounds; D014316:Tritium; D011339:Probenecid; D009638:Norepinephrine; D010130:p-Aminohippuric Acid