Relationship between Para-aminohippurate Secretion and Cellular Morphology in Rabbit Proximal Tubules

We studied indomethacin as a probe of anion transport across the isolated perfused proximal straight tubule of the rabbit and discovered that a substantial component of transport may occur by anion exchange at the basolateral membrane. Various perturbations involving direct or indirect dissipation of the cellular sodium gradient (ouabain, sodium-or potassium-free solutions, cooling to 18°C) resulted in only a 50% inhibition of indomethacin transport, which raised the question of a co-existent alternative pathway for secretion. Similarly, the anion exchange inhibitor, 4,4'-diisothiocyanostilbene (DIDS), diminished indomethacin secretion by only 50%. Cooling followed by DIDS or the reverse sequence resulted in additive inhibition such that the combination abolished active secretion of indomethacin.We conclude that active secretion of indomethacin by the proximal straight tubule appears to be in part sodium gradient dependent; the remainder may be driven by an anion exchanger on the basolateral membrane.

Section: Methodssupporting

confidence: 84%

“…The latter include numerous drugs. There is general agreement that the site of action of organic anion secretion is predominantly the proximal straight renal tubule, in particular the S2 segment (3). In contrast, the mechanism of secretion is much debated.…”

Section: Introductionmentioning

confidence: 99%

Indomethacin secretion in the isolated perfused proximal straight rabbit tubule. Evidence for two parallel transport mechanisms.

Zeeuw

Jacobson²,

Brater³

1988

“…The mean length of the S3 segments was 1.35±0.01 mm (n = 20) in length and therefore some tubules extended into the medullary rays from the outer stripe of the outer medulla, which is -1 mm in thickness. In a previous electron micrographic study of the rabbit proximal tubule, S3 cells were found chiefly in the innermost regions of the cortex and the outer stripe of the outer medulla (37). A large luminal disequilibrium pH was consistently detected independent of which end of the tubule was attached to the collection pipette indicating that the part ofthe proximal straight tubule that lacks carbonic anhydrase is more extensive than just the outer medullary portion of the proximal straight tubule.…”

Section: Resultsmentioning

confidence: 76%

Spontaneous luminal disequilibrium pH in S3 proximal tubules. Role in ammonia and bicarbonate transport.

Kurtz¹,

Star²,

Balaban³

et al. 1986

We determined whether a spontaneous luminal disequilibrium pH, pHdq (pH measured -pH equilibrium), was present in isolated perfused rabbit S2 and S3 proximal tubules. Luminal pH was measured by perfusing with the fluorescent pH probe 1,4-DHPN, and the equilibrium pH was calculated from the measured collected total CO2 and dissolved CO2 concentrations. S2 tubules failed to generate a spontaneous pHdq. S3 tubules generated a spontaneous acidic pH~l of -0.46±0.15 (P < 0.05), which was obliterated following the addition of carbonic anhydrase (0.1 mg/ml) to the perfusate. In S3 tubules perfused and bathed in 4 mM total ammonia, luminal total ammonia rose from 4.08±0.05 mM (perfusate) to 4.95±0.20 mM (collected fluid) (P < 0.02). Carbonic anhydrase added to the perfusate prevented the rise in the collected total ammonia concentration. We conclude that the rabbit S3 proximal tubule lacks functional luminal carbonic anhydrase. The acidic pHd in the S3 segment enhances the diffusion of NH3 into the lumen.-In contrast, the S2 segment has functional luminal carbonic anhydrase.

“…Ouabain did not affect volume reabsorption in SFPCT under condition INTRODUCTION As evidenced by two recent reviews (1, 2) the subject of structural and functional heterogeneity ofnephrons has become a major interest of many investigators of renal physiology. Stimulated by earlier studies documenting anatomical differences between nephrons originating in the superficial and deep cortex (3)(4)(5), recent studies have been aimed at determining whether functional counterparts ofthese anatomic differences exist (6)(7)(8)(9)(10). In a previous in vitro microperfusion study (7) significant intrinsic functional differences were found to exist both between proximal convoluted tubule segments from superficial and juxtamedullary nephrons and between early and later segments of superficial convolutions.…”

mentioning

confidence: 99%

Characteristics of Volume Reabsorption in Rabbit Superficial and Juxtamedullary Proximal Convoluted Tubules

Jacobson¹

1979

A B S T R A C T Segments of superficial and juxtamedullary proximal convoluted tubules of the rabbit were perfused in vitro to examine the mechanisms responsible for net volume reabsorption. The very early postglomerular segments were not studied. Fluid reabsorptive rates and transepithelial potential differences were compared under various conditions: (a) with perfusate that simulated glomerular filtrate; (b) with perfusate that lacked glucose, amino acids, and acetate and that had HCO3 and Cl concentrations of 5 and 140 mM, respectively; (c) with perfusate that lacked glucose, amino acids, and acetate but with 20 meq ofNaHCO3 replaced with 20 meq ofNa cyclamate; (d) with the same perfusate as in b but in the presence of ouabain in the bath; (e) with ultrafiltrate of rabbit serum titrated with HC1 to final HCO3 and Cl concentrations of 2 and 134 mM, respectively. Tubules were perfused with this titrated ultrafiltrate at 37°C, 21°C, and in the presence of 0.1 mM ouabain in the bath. Bath fluid in all experiments was regular rabbit serum. Under conditions a and b superficial proximal convoluted tubule (SFPCT) and juxtamedullary proximal convoluted tubule (JMPCT) behaved similarly with the exception that SFPCT exhibited a lumen-positive and JMPCT a lumen-negative electrical potential under condition b. However, undeT condition c SFPCT failed to exhibit net volume reabsorption, whereas reabsorption in JMPCT continued unchanged. Ouabain did not affect volume reabsorption in SFPCT under condition