Effects of chloride gradients on total CO2 flux in the rabbit cortical collecting tubule

The effects of changes in peritubular pH, carbon dioxide tension (Pco2), and HCO3 concentration on net HCO3 transport was examined in in vitro perfused cortical collecting tubules (CCTs) from unpretreated New Zealand white rabbits. Lowering peritubular HCO3 concentration and pH by reciprocal replacement of HCO3 with Cl-, significantly stimulated net HCO3 absorption. Lowering peritubular HCO3 concentration and pH, by substitution of HCO3 with gluconate, while keeping Cl-concentration constant, also stimulated net HCO3 absorption. Raising peritubular HCO3 concentration and pH, by reciprocal replacement of Cl-with HCO3, inhibited net HCO3 absorption (or stimulated net HCO3 secretion). When the tubule was cooled, raising peritubular HCO3 concentration had no effect on net HCO3 transport, suggesting these results are not due to the passive flux of HCO3 down its concentration gradient.The effect of changes in ambient Pco2 on net HCO3 transport were also studied. Increasing the ambient Pco2 from 40 mmHg to either 80 or 120 mmHg, allowing pH to fall, had no effect on net HCO3 transport. Similarly, lowering ambient Pco2 to 14 mmHg had no effect on net HCO3 transport. Simultaneously increasing peritubular HCO3 concentration and Pco2, without accompanying changes in peritubular pH, i.e., isohydric changes, stimulated net HCO3 secretion to the same degree as nonisohydric increases in peritubular HCO3 concentration. Likewise, isohydric lowering of peritubular HCO3 concentration and Pco2 stimulated net HCO3 absorption.We conclude that: (a) acute changes in peritubular HCO3 concentration regulate acidification in the CCI and these effects are mediated by a transcellular process; (b) acute changes in ambient Pco2 within the physiologic range have no effect on HCO3 transport in the in vitro perfused CCI; and (c) acute in vitro regulation of CCI acidification is independent of peritubular pH.

“…These gradients are smaller than those studied by Laski et al (21). As The next series ofexperiments examined the effects ofaltering ambient Pco2 within the physiologic range.…”

Section: Discussionmentioning

confidence: 80%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Regulation of net bicarbonate transport in rabbit cortical collecting tubule by peritubular pH, carbon dioxide tension, and bicarbonate concentration.

Breyer¹,

Kokko²,

Jacobson³

1986

“…Subsequently, Star et al demonstrated that a 1:1 Cl:HCO3 exchange mechanism is the probable basis for these findings (4). Laski et al (5) proposed that the transepithelial chloride gradient might alter proton secretion by changes in the VTE, or by influencing the apical Cl:HCO3 exchanger.…”

Section: Introductionmentioning

confidence: 99%

Luminal chloride modulates rat distal tubule bidirectional bicarbonate flux in vivo.

Levine¹,

Vandorpe²,

Iacovitti³

1990

The effects of replacing luminal chloride with gluconate on distal tubule bicarbonate transport were studied in vivo in normally fed rats, overnight-fasted rats, and rats made mildly alkalotic by administration of desoxycorticosterone acetate (DOCA). In paired microperfusions of the same tubule with 0 or 55 mM Cl at 25 nl/min, net secretion of bicarbonate by distal tubules of fed rats was inhibited by chloride replacement. Zero chloride perfusion in DOCA rats also resulted in an inhibition of net bicarbonate secretion at 25 nl/min. In contrast, replacement of 45 mM chloride also perfused at 25 nl/min in fasted rats caused an increase in net bicarbonate reabsorption.To further characterize the effects of changes in luminal chloride, experiments were undertaken in fasted rats with 0, 45, and 100 mM chloride-containing solutions perfused at 8 and 25 nI/min. Perfusion with zero Cl resulted in net bicarbonate reabsorption at 8 nl/min that increased markedly with high flow, whereas bicarbonate reabsorption did not change significantly during perfusion at high flow with a 45-mM Cl perfusate. In marked contrast, perfusion with a 100-mM Cl solution resulted in only minimal bicarbonate reabsorption at 8 nl/min with significant secretion observed at high flow.Thus

“…Net HCO3 secretion has been described in cortical collecting tubules dissected from alkali-loaded rats and rabbits (1)(2)(3)(4), but little is known about the hormonal control of this process. Although initial studies by Knepper et al suggested that chronic mineralocorticoid administration stimulates HCO3 secretion by the cortical collecting tubule (5), subsequent investigation has shown that this stimulation is secondary to the accompanying metabolic alkalosis rather than a direct hormonal affect on HCO-transport (6).…”

Section: Introductionmentioning

confidence: 99%

Cyclic adenosine monophosphate-stimulated bicarbonate secretion in rabbit cortical collecting tubules.

Schuster¹

1985

We studied the effects of cyclic AMP (cAMP) on HCO3 transport by rabbit cortical collecting tubules perfused in vitro. Net HCO3 secretion was observed in tubules from NaHCO3-loaded rabbits. 8-Bromo-cAMP-stimulated net HCO3-secretion, whereas secretion fell with time in control tubules. Both isoproterenol and vasopressin (ADH) are known to stimulate adenylate cyclase in this epithelium; however, only isoproterenol stimulated net HCO3 secretion.The mechanism of cAMP-stimulated HCO3 secretion was examined. If both HCO3 and H+ secretion were to occur simultaneously in tubules exhibiting net HCO3-secretion, cAMP might increase the net HCO3-secretory rate by inhibiting H+ secretion, by stimulating HCO3 secretion, or both. These possibilities were examined using basolateral addition of the disulfonic stilbene (4,4'-diisothiocyanostilbene-2,2'-disulfonate (DIDS). In acidifying tubules from NH4Cl-loaded rabbits, DIDS eliminated HCO3-reabsorption, a result consistent with known effects of DIDS as an inhibitor of H+ secretion. In contrast, cAMP left acidification (H+ secretion) intact. DIDS applied to HCO3 secretory tubules failed to increase the HCO3 secretory rate, indicating minimal H+ secretion in HCO3-secreting tubules. Thus, inhibition of H+ secretion by cAMP could not account for the cAMP-induced stimulation of net HCO3 secretion.cAMP-stimulated HCO3 secretion was reversibly eliminated by 0 Cl perfusate, whereas luminal DIDS had no effect. Bath amiloride (1 mM) failed to eliminate cAMP-stimulated HCO3 secretion when bath [Na'J was 145 mM or 5 mM. cAMP depolarized the transepithelial voltage. The collected fluid [HCO3j after cAMP could be accounted for by electrical driving forces, suggesting that cAMP stimulates passive HCO3 secretion. However, cAMP did not alter HCO3 permeability measured under conditions expected to inhibit transcellular HCO3 movement (O Cl-solutions and bath DIDS). This measured HCO3 permeability was not high enough to account, by passive diffusion, for the HCO3 fluxes observed in Cl--containing solutions.We conclude the following: 1) cAMP increased net HCO3 secretion by stimulating HCO3 secretion and not by