Comparison of calcium and sodium transport in early and late rat distal tubules: effect of amiloride

Abstract

In vivo tubular microperfusion experiments were performed in rats to compare the function of the early and late rat distal convoluted tubule and to examine the effect of amiloride on distal Na and Ca reabsorption. In clearance experiments, amiloride (6 micrograms/min) reduced fractional Ca excretion (P less than 0.05) and the calcium-to-sodium clearance ratio (P less than 0.001) without affecting fractional Na excretion. The in vivo microperfusion experiments revealed a higher rate of osmotic water flow in late distal convoluted tubules than in early tubules (P less than 0.001), while Na and Ca transport rates were comparable. The addition of 10(-5) M amiloride to the luminal perfusate inhibited net fluid reabsorption (P less than 0.05) and Na reabsorption (P less than 0.01) and enhanced Ca reabsorption (P less than 0.005) in late segments of the distal tubule. The drug did not change early distal function. The degree of enhancement of Ca transport was highly correlated with the degree of inhibition of Na transport, suggesting that the two effects are related. We suggest that increased Ca reabsorption is a result of luminal membrane hyperpolarization or of increased rates of Ca-Na exchange.

Vasopressin-stimulated Ca 2+ reabsorption in rabbit cortical collecting system: effects on cAMP and cytosolic Ca 2+

“…On the contrary, the slightly stimu latory effect of benzamil on basal Ca2* transport suggests that Na* entry rather exerts a negative feedback on Ca2* transport. Similar stimulatory effects of amiloride ana logues on active Ca2* reabsorption have been reported in literature [12]. One explanation for this finding might be that the activity of the basolateral Na*-Ca2* exchanger, which plays an important role in transepithclial Ca2* transport [4], is already inhibited at basal intracellular Na* levels.…”

Functional Domains of the Epithelial Sodium Channel

“…In general, amiloride-sensitive currents decreased in the following order: CNT Ͼ initial CD Ͼ CD (13). These findings on apical ENaC localization and activity are consistent with previous studies on microperfused rat tubules (14,15) and on isolated rabbit tubules (16) that established several times higher sodium transport rates in early ASDN (DCT and CNT) than in ASDN segments farther downstream (CD), and also with studies that showed a progressive decrease of the basolateral Na-K-ATPase activity along the ASDN (17). Taken together, the data clearly suggest that the aldosterone-dependent adaptation of renal sodium excretion to dietary sodium intake occurs predominately in the early ASDN, whereas the late ASDN gets recruited only under high plasma aldosterone levels.…”

Dietary Sodium Intake Regulates the Ubiquitin-Protein Ligase Nedd4-2 in the Renal Collecting System

“…It is most pronounced in the early ASDN portions (late DCT and early CNT) and progressively decreases along further downstream localized segments (late CNT and CD) (2,6). This morphologically ascertainable gradient is consistent with numerous functional studies showing several-fold higher transepithelial Na ϩ transport rates and ENaC activity in the CNT than in the CD (7)(8)(9)(10)(11). However, the underlying molecular mechanisms for this axial heterogeneity are unclear.…”

“…Whereas Nedd4-2 immunostaining increased along the axis of the ASDN, apical ENaC localization decreased. The axial gradient of apical ENaC localization was seen in several species and was evident also in microperfusion, micropuncture, and patch-clamp studies that showed much higher ENaC activity in early ASDN (i.e., the CNT) than in late ASDN segments (i.e., the CD) (2,(7)(8)(9)(10)(11)29). Differences in the expression levels of mineralocorticoid receptor 11-␤HSD2 and SGK1 likely do not account for this axial heterogeneity, because these ENaC-regulating molecules seem to be equally abundant along the CNT and CCD (reviewed in [(47]).…”