Further studies in deoxycorticosterone acetate treated rats: brain content of mineralocorticoid and glucocorticoid receptors and effect of steroid antagonists on salt intake.
We have studied the role of mineralocorticoid receptors (MR) and glucocorticoid receptors (GR) on salt appetite developed by deoxycorticosterone acetate (DOCA) treated rats. To this end, we measured the effects of DOCA given on alternate days on (1) salt intake; (2) MR and GR in hippocampus (HIPPO), amygdala (AMYG), and hypothalamus (HT); (3) the activity of ornithine decarboxylase (ODC), a GR-mediated response, and (4) the salt intake after treatment with the antiglucocorticoid RU 486 or the antimineralocorticoid ZK 91587. First, we demonstrated that 10 but not 1 mg DOCA induced natriogenesis. Forty-eight hours after adrenalectomy and 24 h after the last DOCA injection, 10 but not 1 mg hormone reduced binding to GR in HIPPO, AMYG, and HT. Both doses of DOCA also reduced the binding to MR in HIPPO, without changes in AMYG; in HT the 1-mg dose was without effect, but the natriogenic dose (10 mg) highly increased binding of [3H]-corticosterone to MR. Scatchard analysis demonstrated increased Bmax and Kd values in the HT of DOCA-treated rats. Occupation of GR by DOCA did not stimulate the ODC activity, in contrast to the four-fold increment effected by the glucocorticoid dexamethasone. Also, administration of RU 486 did not inhibit the sale intake promoted by DOCA, in contrast to ZK 91587 which partly delayed the natriogenic effect of DOCA. It is suggested that brain MR are involved in the natriogenic effect of DOCA, whereas the role of GR is inconclusive.(ABSTRACT TRUNCATED AT 400 WORDS)
Vallee
S M
SM
Laboratory of Neuroendocrine Biochemistry, Instituto de Biología y Medicina Experimental, Buenos Aires, Argentina.
Grillo
C A
CA
Gonzalez
S
S
Cosen-Binker
L
L
de Kloet
E R
ER
McEwen
B S
BS
De Nicola
A F
AF
D000679:Amygdala / Q000187:drug effects; D000818:Animals; D001066:Appetite / Q000187:drug effects*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D003900:Desoxycorticosterone / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects; D007031:Hypothalamus / Q000187:drug effects; D008297:Male; D015735:Mifepristone / Q000494:pharmacology; D000451:Mineralocorticoid Receptor Antagonists; D009955:Ornithine Decarboxylase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011965:Receptors, Glucocorticoid / Q000037:antagonists & inhibitors / Q000502:physiology*; D018161:Receptors, Mineralocorticoid / Q000502:physiology*; D017673:Sodium Chloride, Dietary / Q000008:administration & dosage*; D013148:Spironolactone / Q000031:analogs & derivatives / Q000494:pharmacology
D000451:Mineralocorticoid Receptor Antagonists; D011965:Receptors, Glucocorticoid; D018161:Receptors, Mineralocorticoid; D017673:Sodium Chloride, Dietary; D013148:Spironolactone; D015735:Mifepristone; D003900:Desoxycorticosterone; C054537:ZK 91587; D009955:Ornithine Decarboxylase