1. Conventional
microelectrodes, the Na+ channel blocker
amiloride (0.1 mM), and the K+ channel blocker
tetraethylammonium chloride (
TEA, 30 mM) were used to examine the effects of
corticosteroid hormones administered in vivo on the Na+ and K+ transport properties of isolated rat distal colon. The cell membrane changes induced by
aldosterone (a specific
mineralocorticoid),
RU 28362 (a synthetic
glucocorticoid with negligible affinity for
mineralocorticoid receptors), and
dexamethasone (an activator of both
mineralocorticoid and
glucocorticoid receptors) were compared. 2. In control animals, there was no
amiloride-sensitive apical Na+ conductance, and only a relatively small
TEA-sensitive apical K+ conductance. 3.
Hyperaldosteronism secondary to dietary Na+ depletion for 10-14 days,
dexamethasone (600 micrograms 100 g-1 day-1 for 3 days), and
RU 28362 (600 micrograms 100 g-1 day-1 for 3 days) induced
amiloride-sensitive electrogenic Na+ transport, with the potency of
aldosterone greater than
dexamethasone greater than
RU 28362. 4. With each
corticosteroid, increased electrogenic Na+ transport reflected enhanced apical Na+ conductance, and in the case of
aldosterone and
dexamethasone, 3.3-fold and 2-fold increases respectively in the maximum activity of the basolateral Na+-K+ pump. In contrast,
RU 28362 suppressed the maximum activity of the basolateral Na+-K+ pump by 45%. 5. All three
corticosteroids enhanced the K+ conductance of the apical membrane, with the potency of
aldosterone greater than
dexamethasone greater than
RU 28362. 6. Co-administration of
spironolactone (5 mg 100 g-1 day-1) inhibited the effects of
aldosterone on Na+ and K+ transport, but in
dexamethasone-treated animals
spironolactone resulted in a pattern of response similar to that found in RU 28362-treated animals. 7. The results support the view that
mineralocorticoid receptors mediate changes in colonic Na+ and K+ transport which differ quantitatively and qualitatively from those mediated by
glucocorticoid receptors.
Dexamethasone and similar '
glucocorticoids' activate both types of receptor, with an overall epithelial response which mimics that induced by
aldosterone.