Effect of aldosterone on ion transport by rabbit colonIn vitro

Abstract

Segments of descending colon obtained from rabbits, that had been maintained on drinking water containing 25 mM NaCl and an artificial diet which contains 1% Na and is nominally K-free, respond to aldosterone in vitro (after a 30 to 60-min lag period) with a marked increase in the short-circuit current (Isc), an equivalent increase in the rate of active Na absorption (JNa net) and a decline in tissue resistance (Rt). Aldosterone also brings about a marked increase in the unidirection influx of Na into the cells across the mucosal membrane ("zero-time" rate of uptake) which does not differ significantly from the inrease m Isc. Treatment of control tissues with amphotericin B brings about sustained increases in Isc and JNa net to levels observed in aldosterone-treated tissues. However, addition of amphotericin B to the mucosal solution of aldosterone-treated tissues does not result in a sustained increase in Isc or JNa net and these values do not differ markedly from those observed in control tissues treated with amphotericin B. These findings, together with other evidence that Na entry in the presence of amphotericin B is sufficiently rapid to saturate the active Na extrusion mechanism at the baso-lateral membrane, are consistent with the notion that the aldosterone-induced protein increases the permeability of the mucosal membrane to Na but does not increase the "saturation level" of the active Na "pump" within the time-frame of these studies (3 hr). Finally, aldosterone has no effect on the bidirectional or net transepithelial movements of K under short-circuit conditions, suggesting that the enhanced secretion of K observed in vivo is the result of increased diffusion of K from plasma to lumen via paracellular pathways in response to an increased transepithelial electrical potential difference (lumen negative).

Effects of corticosteroid hormones on the electrophysiology of rat distal colon: implications for Na+ and K+ transport.

“…Because the specific glucocorticoid RU 26988 has been shown to increase distal colonic Na+ absorption, K+ secretion, and in vivo transmucosal potential difference in adrenalectomized animals (Bastl et al 1984), suppression of Na+-K+ pump activity by RU 28362 was an unexpected finding. One explanation for this paradox may be that sufficient pump activity remained in the RU 28362-treated tissues to accommodate the increase in apical Na+ entry, as studies in rabbit descending colon 436 CORTICOSTEROIDS AND COLONIC CATION TRANSPORT indicate that the basolateral Na+-K+ pump normally operates at -50% of its maximum capacity (Frizzell & Schultz, 1978). In the rat, plasma levels of corticosterone exceed those of aldosterone by several order of magnitude (Martin et al 1983), and corticosterone binds to mineralocorticoid receptors as well as to glucocorticoid receptors (Marusic et al 1981;Lan, Graham, Bartter & Baxter, 1982 Na+-depleted than in dexamethasone-treated animals (Foster et al 1983).…”

“…Stimulation of rat distal colon by aldosterone for 3-7 days or longer further enhances amiloride-sensitive electrogenic Na+ transport and completely inhibits amiloride-insensitive electroneutral NaCl absorption (Foster et al 1983;Halevy et al 1986). Experimental evidence from several sources suggests that the increases in basolateral membrane area and Na+, K+-ATPase content induced by chronic hyperaldosteronism (Kashgarian, Taylor, Binder & Hayslett, 1980) are secondary to a sustained increase in apical Na+ entry rather than a direct effect of aldosterone on the basolateral membrane (Frizzell & Schultz, 1978;Will, DeLisle, Cortright & Hopfer, 1981;Halm & Dawson, 1985; Halevy, Boulpaep, . Consequently, hyperpolarization of the basolateral membrane observed in the aldosterone-treated tissues may reflect a rise in intracellular K+ concentration owing to increased basolateral K+ uptake, as we have demonstrated that Vb, intracellular K+ concentration, and basolateral Na+,K+ ATPase activity increase in parallel in two other models of secondayry hyperaldosteronism, namely chronic 12-fold dietary K+ enrichment in renal-intact animals, and chronic 4-fold dietary K+ enrichment in partially nephrectomized animals (Sandle, Foster, Lewis, Binder & Hayslett, 1985;Sandle, McGlone & Davies, 1988).…”

“…The initial epithelial response is rapid, and stimulation of Na+ and K+ transport is evident in distal colon of rabbit, rat and man 1-5 h after in vivo or in vitro exposure to mineralocorticoid or glucocorticoid hormones (Binder, 1978;Frizzell & Schultz, 1978;Sandle, Hayslett & Binder, 1986;Sandle & McGlone, 1987a;Bridges, Rummel & Schreiner, 1987). Specific receptors for corticosteroid hormones are present in the cytosol of colonic epithelial cells (Bastl, Barnett, Schmidt & Litwack, 1984;Binder, White, Whiting & Hayslett, 1986), and changes in Na+ and K+ transport are the end-result of a sequence of events which involves the formation of an 'activated' hormone-receptor complex, movement of the complex to intranuclear binding sites, and the induction of transport proteins which ultimately appear in the cell membrane (Edelman, 1981;Schmidt & Litwack, 1982).…”

Physiologic and Pharmacologic Effects of Glucocorticoids on Ion Transport across Rabbit Ileal Mucosa In Vitro

“…Thus, while direct evidence is not available, it is likely that glucocorticoids stimulate electrogenic Na absorption in the ileum primarily by increasing the Na permeability of the brush border membrane. Both under basal conditions and with glucocorticoid enhancement, ileal Na permeability was amiloride insensitive, which contrasts with the amiloride-sensitive nature of both basal and mineralocorticoid-stimulated Na transport in distal colon (3).…”

“…Glucocorticoids at pharmacologic dosage have been shown to increase Na, K-activated ATPase activity in homogenates from both small and large intestine of the rat, but, in the colon at least, this effect does not become apparent until long after there is a demonstrable increase in transmural PD and Na absorption in vivo (40). Furthermore, Na pump capacity is not ordinarily rate-limiting in either small or large intestine because agenits that act initially or exclusively at the luminal Glucocorticoids and hleal Ioni Trantsport border, such as glucose and amphotericin, cause a rapid increase in Na transport (3,21). Thus, while direct evidence is not available, it is likely that glucocorticoids stimulate electrogenic Na absorption in the ileum primarily by increasing the Na permeability of the brush border membrane.…”