Differential effects of corticosteroids on Na+ transport in rat distal colon in vitro

Abstract

We studied rat distal colon during in vitro incubation with aldosterone and dexamethasone. Both hormones caused short-circuit current (Isc) to increase with a latency period of approximately 3 h. At the 7th h of incubation, control colons had a Isc of 72 +/- 8 microA . cm-2 while tissues incubated with 10(-5) M aldosterone and 10(-8) M dexamethasone, the respective maximal stimulatory concentrations, had similarly increased Isc, 211 +/- 21 and 185 +/- 18 microA . cm-2, respectively. The increase in Isc induced by steroids reflected increased net sodium transport: control, 3.4 +/- 0.8; aldosterone, 6.7 +/- 0.7 (P less than 0.05); and dexamethasone, 7.5 +/- 1.0 mueq . h-1 . cm-2 (P less than 0.025). Spironolactone inhibited the response to both steroids, but the molar ratio of antagonist to agonist was less for aldosterone (approximately 5,000:1) than for dexamethasone (approximately 50,000:1). Amiloride inhibited a greater fraction of aldosterone-induced Isc (0.70 +/- 0.07) than that of dexamethasone (0.37 +/- 0.07; P less than 0.025). The latter value was similar to the effect of amiloride on control tissues (0.35 +/- 0.04). These data provide evidence that the cellular mechanisms by which aldosterone and dexamethasone induce Na+ transport are different.

Effects of acid-base variables on ion transport in rat colon.

“…It is also likely that the relatively large chamber volume and unpaired design of the HCO3 experiments limited our ability to detect small changes in net HCO3 secretion. This is especially relevant in light of the recent finding, using a new in vitro technique, that extracellular HCO3 concentration apparently does modulate active colonic HCO3 secretion (9,34). For these reasons, our conclusions regarding the effects ofHCO3 concentration and various inhibitors on JR and HCO3 secretion by the colon must be tentative.…”

“…The distal colon of the rat is of particular interest in this regard, because its electrolyte transport systems are well characterized (4)(5)(6)(7)(8)(9), and its response to arterial Pco2 and HCO3 concentration is specific and spans the physiological range of values for these variables. As in other transporting epithelia, the effects of CO2 apparently were mediated through changes in the intracellular pH (pHi)' of the colonic epithelium (10,11), and were dependent on mucosal carbonic anhydrase activity (12).…”

Effects of resalination on intestinal glucose transport in chickens adapted to low Na+ intakes

“…However, in the present study the changes in the hexose transport properties of the apical and basolateral membranes follow a similar pattern, suggesting that some common step in the regulatory cascade enables the simultaneous incorporationÏ activation of both SGLT1 and GLUT2 after the resalination. Aldosterone has been shown to rapidly (within 1-3 h) increase the Na¤-K¤-ATPase activity in the kidney (Jorkasky et al 1985) and it has been postulated that it is not the number but the activity of the pumps that is regulated. In the case of membrane glucose transporters, low-Na¤ adaptation changes the uptake rate (as indicated by the Vmax) and the number of transporters (as indicated by the binding of phlorizin and cytochalasin B), and when animals are resalinated both function and number are also increased in a short time.…”

Mechanisms of Colonic Electrolyte Absorption and Secretion

“…Recent studies have sug gested that the overall changes in colonic electrolyte transport resulting from chronic administration of pharmacological doses of glucocorticoids (e.g. méthylprednisolone, dexamethasone) are similar to those induced by mineralocorticoids [48,[53][54][55], Since high doses of dexamethasone bind to miner alocorticoid receptors [56], the question arises as to whether glucocorticoids produce their effects by activating mineralocorticoid receptors, by activating specific glucocorti coid receptors, or by activating both types of corticosteroid receptor. In rat distal colon, aldosterone has been shown to inhibit elec troneutral NaCl absorption, stimulate elec trogenic Na absorption, and change K trans port from net K absorption to net K secre tion [5], whereas dexamethasone has no ef fect on electroneutral NaCl absorption, is less effective in stimulating electrogenic Na absorption, and changes net K. transport to zero [5].…”