M. Paillard

Polarized Expression of Different Monocarboxylate Transporters in Rat Medullary Thick Limbs of Henle

Extracellular lactic acid is a major fuel for the mammalian medullary thick ascending limb (MTAL), whereas under anoxic conditions, this nephron segment generates a large amount of lactic acid, which needs to be excreted. We therefore evaluated, at both the functional and molecular levels, the possible presence of monocarboxylate transporters in basolateral (BLMVs) and luminal (LMVs) membrane vesicles isolated from rat MTALs. Imposing an inward H+ gradient induced the transient uphill accumulation of l-[14C]lactate in both types of vesicles. However, whereas the pH gradient-stimulated uptake ofl-[14C]lactate in BLMVs was inhibited by anion transport blockers such as α-cyano-4-hydroxycinnamate, 4,4′-diisothiocyanatostilbene-2,2′-disulfonic acid (DIDS), and furosemide, it was unaffected by these agents in LMVs, indicating the presence of a l-lactate/H+ cotransporter in BLMVs, but not in LMVs. Under non-pH gradient conditions, however, the uptake of l-[14C]lactate in LMVs was transstimulated 100% by l-lactate, but by only 30% byd-lactate. Furthermore, this l-lactate self-exchange was markedly inhibited by α-cyano-4-hydroxycinnamate and DIDS and almost completely by 1 mm furosemide, findings consistent with the existence of a stereospecific carrier-mediated lactate transport system in LMVs. Using immunofluorescence confocal microscopy and immunoblotting, the monocarboxylate transporter (MCT)-2 isoform was shown to be specifically expressed on the basolateral domain of the rat MTAL, whereas the MCT1 isoform could not be detected in this nephron segment. This study thus demonstrates the presence of different monocarboxylate transporters in rat MTALs; the basolateral H+/l-lactate cotransporter (MCT2) and the luminal H+-independent organic anion exchanger are adapted to play distinct roles in the transport of monocarboxylates in MTALs.

Determinants of Parathormone Secretion in Primary Hyperparathyroidism

We studied the effects of acute modifications in plasma calcium on parathormone (PTH) secretion in 23 patients with primary hyperparathyroidism (PHPT). In 12 patients, PTH hypersecretion was autonomous, and basal plasma calcium concentration was positively correlated with maximal serum PTH(1-84) reached during Na2EDTA infusions. In 11 patients, PTH hypersecretion remained suppressible, but with elevated set point value, and basal plasma calcium concentration was positively correlated with set point. Thus, the degree of hypercalcemia seems mainly determined by the magnitude of maximal PTH secretion and set point error in autonomous and suppressible PHPT, respectively. We have previously suggested that high serum calcitriol levels might chronically inhibit PTH hypersecretion in PHPT. We showed that hyperparathyroid patients with renal stone presentation exhibited an abnormally high value of circulating calcitriol and a moderately elevated PTH activity, while patients with severe bone disease presentation displayed a low to normal calcitriol value and a dramatically increased PTH activity. The hypothesis was supported by a recent study from our Unit in one hyperparathyroid patient with severe bone disease and normal serum calcitriol level. Increment of serum calcitriol after daily intravenous Rocaltrol for 5 days directly suppressed PTH hypersecretion without change in plasma ionized calcium.

Potassium dependent H+/HCO3- transport mechanisms in cells of medullary thick ascending limb of rat kidney

The medullary thick ascending limb (mTAL) of rat kidney has been recently shown to absorb bicarbonate at substantial rate and to contribute to acidification of the final urine (5).

Mechanisms of H+/HCO3− Transport in Rat Kidney Medullary Thick Ascending Limb. Effects of Arginine Vasopressin

The thick ascending limb (TAL) of rat kidney absorbs bicarbonate and substantial rates (Good et al. 1984) that may account for much of the bicarbonate absorbed from Henle’s loop in vivo (about 15% of the bicarbonate filtered load, Bichara et al. 1984). Yet, the cellular mechanisms of H+/HCO3 − transport by the rat TAL have been studied in only a few studies that have reported in the cortical segment the presence of a luminal Na+:H+ antiport (Good 1985) and of a basolateral Na+: (HCO3 −)n>1 symport (Krapf 1988). Also, in the medullary segment (MTAL) of the mouse TAL, a luminal Na+:H+ antiport and a basolateral Na+:(HCO3 −) n >1 symport have been described (Kikeri et al. 1990).