|
|
||||||||
1 Institut für Klinische Physiologie and 2 Medizinische Klinik I Gastroenterologie und Infektiologie, Universitätsklinikum Benjamin Franklin, Freie Universität Berlin, D-12200 Berlin, Germany
The potency of in vitro-added corticosteroids to
stimulate electrogenic Na+
absorption (JNa,
the Na+ absorptive short-circuit
current blockable by 10
4 M
amiloride) was determined in rat late distal colon.
JNa was determined 8 h after steroid addition from the drop in short-circuit current caused by 10
4 M
amiloride. The concentration dependency of
JNa was obtained for seven corticosteroids and compared with that established for aldosterone. Apparent mineralocorticoid potencies as determined from
apparent Michaelis-Menten constant
(Km) values
were as follows: aldosterone 1.2 nM
RU-28362 20 nM = deoxycorticosterone 20 nM > deoxycortisol 36 nM
dexamethasone 37 nM
corticosterone 170 nM > cortisol 210 nM. These
steroids exhibited Vmax values of 9-13
µmol · h
1 · cm
2
and similar concentration dependencies. Hill coefficients were between
1.6 and 2.1, suggesting cooperative effects between activated receptors. We conclude that corticosteroids exhibit graded
mineralocorticoid potency instead of a sharp partition into exclusive
groups of mineralocorticoid and nonmineralocorticoid hormones. The low
apparent Km value
of RU-28362 for mineralocorticoid action and the need for high
concentrations of the mineralocorticoid antagonist mespirenone to block
this response indicated that
JNa in a native
mammalian epithelium can be mediated by the glucocorticoid receptor.
Glucocorticoid receptor-specific amounts of RU-28362 in combination
with mineralocorticoid receptor-specific amounts of aldosterone or of
the mineralocorticoid antagonist spironolactone showed cooperative
action, suggesting a heterodimeric activation of
JNa by the
glucocorticoid receptor and mineralocorticoid receptor.
short-circuit current; corticosterone; RU-28362; spironolactone; heterodimerization
This article has been cited by other articles:
![]() |
H J Novaira, D S Ornellas, T M Ortiga-Carvalho, X M Zhang, J Souza-Menezes, S E Guggino, W B Guggino, and M M Morales Atrial natriuretic peptide modulates cystic fibrosis transmembrane conductance regulator chloride channel expression in rat proximal colon and human intestinal epithelial cells. J. Endocrinol., April 1, 2006; 189(1): 155 - 165. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. M. Hoque, V. M. Rajendran, and H. J. Binder Zinc inhibits cAMP-stimulated Cl secretion via basolateral K-channel blockade in rat ileum Am J Physiol Gastrointest Liver Physiol, May 1, 2005; 288(5): G956 - G963. [Abstract] [Full Text] [PDF] |
||||
![]() |
J C J Oprins, C van der Burg, H P Meijer, T Munnik, and J A Groot Tumour necrosis factor {alpha} potentiates ion secretion induced by histamine in a human intestinal epithelial cell line and in mouse colon: involvement of the phospholipase D pathway Gut, March 1, 2002; 50(3): 314 - 321. [Abstract] [Full Text] [PDF] |
||||
![]() |
H. J. Epple, S. Amasheh, J. Mankertz, M. Goltz, J. D. Schulzke, and M. Fromm Early aldosterone effect in distal colon by transcriptional regulation of ENaC subunits Am J Physiol Gastrointest Liver Physiol, May 1, 2000; 278(5): G718 - G724. [Abstract] [Full Text] [PDF] |
||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |