摘要:

Recent evidence suggests that vasopressin exerts a regulatory influence on transport processes in the rabbit cortical collecting duct via both the baso-lateral and luminal membranes. The present study was undertaken to examine whether luminal vasopressin receptors, coupled to changes in intracellular calcium, were also present in microperfused rat medullary thick ascending limb (mTAL), a key element of the urine concentrating mechanism. Addition of 1 nM vasopressin to the luminal microperfusate elicited a small but significant and sustained rise in intracellular calcium, from basal values of 100.1 ± 20.1 to 169.6 ± 24.1 nM after 250 s. The effect observed following luminal addition of vasopressin was dose-dependent, with a larger increment of 190.2 ± 32.2nM evoked by addition of 1 µM vasopressin. Addition of 1 µM oxytocin to the lumen did not cause a significant increase in intracellular calcium concentration, consistent with the response to vasopressin being mediated by specific luminal vasopressin receptors. In the absence of calcium in the bath and lumen together or in the bath alone, a residual response to 1 µM luminal vasopressin was still evident, suggestive of a small component of release of calcium from intracellular stores. Selective calcium removal from the luminal microperfusate alone left the response intact. These data are congruous with a model of vasopressin-induced entry of calcium which occurs via the basolateral membrane following ligand binding to the apical membrane. These findings, coupled with earlier observations in the collecting duct, suggest that a fundamental re-assessment of where and how vasopressin, and perhaps other hormones, acts in the kidney may be required. Hormonal regulation of distal tubular function may not therefore be determined only by blood-borne delivery of hormone, but may also involve tubular fluid delivery to apical receptors in distal nephron

ISSN:1420-4096    

DOI:10.1159/000173782

出版商:S. Karger AG    

年代:1994

数据来源: Karger

摘要:

Renal clearance and tubule microperfusion experiments were carried out to investigate the effects of chronic potassium depletion upon the renal response to furosemide. Rats kept on a potassium-deficient diet for 3 weeks developed hypokalemia, metabolic alkalosis, and decreased aldosterone levels. These rats responded to an oral administration of furosemide (32 mg/ kg) with a blunted excretion rate of urine and sodium. Whereas furosemide increased fractional urine sodium excretion to 5.2% in control rats, the corresponding rate in potassium-depleted rats was 2.8%. The urinary excretion of furosemide was also significantly reduced during potassium depletion from 3.06 mg/kg in control rats to 0.97 mg/kg in potassium-depleted rats. In separate experiments, loops of Henle were pump-perfused with furosemide-containing solutions in control and potassium-depleted rats. No major modification of the inhibitory effects of furosemide on sodium transport was observed when the potassium concentration of the perfusion fluid was kept at the low levels expected in hypokalemic rats. Metabolic alkalosis unaccompanied by potassium deprivation did not decrease the diuretic response to furosemide. These experiments indicate that potassium deprivation reduces the diuretic effects of furosemide by mechanisms including diminished furosemide delivery to its tubule site of action.

ISSN:1420-4096    

DOI:10.1159/000173783

出版商:S. Karger AG    

年代:1994

数据来源: Karger

摘要:

This study was designed to measure H-K-ATPase and Na-K-ATPase activities in rat inner medullary collecting duct (IMCD) cells during potassium depletion and loading. Both enzyme activities were similarly distributed from the proximal to the distal portion of this nephron segment. One week K depletion did not stimulate H-K-ATPase activity but reduced Na-K-ATPase activity. Within 2 weeks after the onset of potassium depletion, the rats developed metabolic alkalosis, and H-K-ATPase activity was suppressed while Na-K-ATPase activity had returned to control values. H-K-ATPase activity was suppressed following potassium loading whereas Na-K-ATPase activity was unchanged. The results are consistent with the presence of H-K-ATPase in IMCD and indicate that H-K-ATPase and Na-K-ATPase activities are modulated by potassium intake.

ISSN:1420-4096    

DOI:10.1159/000173784

出版商:S. Karger AG    

年代:1994

数据来源: Karger

摘要:

The active pump mechanisms involved in K+ secretion of the malpighian tubules of the ant and present in the luminal membrane were investigated on isolated, luminally perfused tubules of Formica. The specific blocker for vacuolar type ATPases, bafilomycin A1, was found to half-maximally inhibit secretion at a concentration of 10-5 mol/l when added to the lumen. N-Ethylmaleimide reduced the calculated short circuit current (Isc) to 78 and 21% of control value when added at 5 · 10-4 mol/l, respectively, to the lumen and the bath. Reducing luminal pH inhibited Isc with a half-maximal inhibition at a luminal pH of 4.5. Acidified omeprazole, Schering compound 28080 and vanadate (both 10-3 and 10-4 mol/l) inhibited Isc only partially. The present data suggest that the luminal membrane of ant malpighian tubules contains a H+ pump. This pump is only poorly bafilomycin-sensitive. Furthermore, additional active transport systems responsible for secretion may be present. Part of these results have been published as abstracts

ISSN:1420-4096    

DOI:10.1159/000173785

出版商:S. Karger AG    

年代:1994

数据来源: Karger

摘要:

The proximal tubule of the kidney is regarded the main intrarenal target of the nephrotoxin Ochratoxin A (OTA). To gain further insight into the importance of the proximal tubule we investigated renal p-aminohippurate (PAH), inorganic phosphate (P), amino acid (AA) and OTA handling in male Wistar rats. The acute application of OTA (1.2 mg/kg) did not affect the renal handling of any of the substances investigated in contrast to the acute effect of OTA on ‘postproximal parts of the nephron. Application of OTA (0.5 mg&slash;(kg·day)) over 6 days resulted in a dramatic decrease of the transport maximum of PAH (reduction to 15% of control) and to an increase of the apparent affinity of PAH to the organic anion transporter. Absolute excretion of P was not increased, whereas - due to the reduced GFR - the fractional excretion (FE) increased (to 180% of control). FE of the AA was not affected by OTA. Free-flow micropuncture experiments performed in L-homoarginine-loaded rats - to unmask possible small alterations of the amino acid transport kinetics - revealed that the proximal tubular transport of amino acids is not impaired by OTA. Subchronic exposure of the animals to OTA reduced the excretion of the mycotoxin itself to about 15% of controls. We conclude that the proximal tubule is not the main but one important intrarenal target of subchronically applied OTA. Furthermore, the action of OTA on the proximal tubule leads to decreased capacity to eliminate OTA possibly resulting in a self-enhancing eff

ISSN:1420-4096    

DOI:10.1159/000173786

出版商:S. Karger AG    

年代:1994

数据来源: Karger

摘要:

The corticosteroid, triamcinolone, was examined as a potential antagonist for the nephrotoxicity of cisplatin in female Wistar rats. The changes in renal function and renal morphology were assessed on the 3rd day after administration of cisplatin (7.5 mg/kg BW) and in animals given triamcinolone retard (4 mg/kg BW) 6 h before administration of cisplatin. Pretreatment with triamcinolone resulted in much less severe changes in renal function after cisplatin administration (serum urea: triamcinolone plus cisplatin 14.29 ± 1.90 mg/l, cisplatin alone 21.60+2.34 mg/l, p < 0.05, control 2.78 ± 0.19 mg/l, serum creatinine: triamcinolone plus cisplatin 0.21 ± 0.02 mg/l, cisplatin alone 0.30 ± 0.02 mg/l, p < 0.05, control 0.06 ± 0.01 mg/l). In contrast to cisplatin-treated animals in triamcinolone-pretreated rats alterations of water content were found neither in renal cortex (triamcinolone plus cisplatin 3.39 ± 0.16g/g dry weight, cisplatin alone 4.07 ± 0.07g/g dry weight, control 3.07 ± 0.07 g/g dry weight) nor in outer medulla (triamcinolone plus cisplatin 4.20 ± 0.22 g/g dry weight, cisplatin alone 4.98 ± 0.21 g/g dry weight, control 3.84 ± 0.11 g/g dry weight) compared to control. The structure of the kidney following cisplatin administration demonstrated extensive lesions of S3 segments of the proximal tubule. The changes in proximal convoluted tubules were widespread and ranged from the decrease of the amount of microvilli to loss of brush border or even to cell death. In triamcinolone-pretreated rats the structure of the cortex appeared to be virtually normal and tissue of medulla was only sligh

ISSN:1420-4096    

DOI:10.1159/000173787

出版商:S. Karger AG    

年代:1994

数据来源: Karger