Effects of deoxycorticosterone acetate (DOCA) and aldosterone on Sar1-angiotensin II binding and angiotensin-converting enzyme binding sites in brain.
1. It is known that regulation of salt appetite is a complex behavior controlled in the brain by interaction of mineralocorticoids (MC) and angiotensin II (ANGII). To investigate the effects of MC on ANGII receptors and ANGII synthesis, we have studied two models of salt appetite control. 2. In the first model, doses of DOCA sufficient to induce salt appetite of intact rats were given. In the second one, we studied the effects of aldosterone (ALDO) in doses sufficient to suppress salt appetite developed by prior adrenalectomy (ADX). 3. Binding to ANGII receptors was determined in brain sections incubated with 3 nM [125I]Sar1 ANGII, exposed to [3H]Hyperfilm with an optical density of autoradiograms measured by computerized densitometry. Sar1-ANGII binding was increased by DOCA treatment in the median preoptic nucleus (MnPO) and subfornical organ (SFO) but not in the paraventricular nucleus (PVN) in comparison to vehicle-treated rats. ALDO treatment was without effect on the MnPO but increased ANGII binding in the SFO and PVN. Neither hormone affected binding in the median eminence or anterior pituitary (AP). 4. In contrast to effects on Sar1-ANGII binding in selected areas, [125I]351A binding to angiotensin-converting enzyme (ACE) was unchanged by DOCA or ALDO administration in the SFO, caudate putamen, AP, or posterior pituitary. 5. These findings suggest that MC modulation of the renin-angiotensin system is exerted at the central, and not at the pituitary level. ANGII receptors were modulated in a dose- and region-specific manner: while DOCA may promote their actions upon the MnPO and SFO, ALDO actions may occur at the PVN and SFO. This mechanism may not require increased generation of ANGII in the brain or pituitary.
De Nicola
A F
AF
Laboratory of Neuroendocrine Biochemistry, Instituto de Biología y Medicina Experimental, Buenos Aires, Argentina.
Seltzer
A
A
Tsutsumi
K
K
Saavedra
J M
JM
D000315:Adrenalectomy; D000450:Aldosterone / Q000494:pharmacology*; D000704:Analysis of Variance; D000804:Angiotensin II / Q000031:analogs & derivatives* / Q000378:metabolism; D000818:Animals; D001345:Autoradiography; D001665:Binding Sites; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D003900:Desoxycorticosterone / Q000494:pharmacology*; D007457:Iodine Radioisotopes; D008297:Male; D009928:Organ Specificity; D007703:Peptidyl-Dipeptidase A / Q000187:drug effects / Q000378:metabolism*; D010902:Pituitary Gland / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011945:Receptors, Angiotensin / Q000378:metabolism*
D007457:Iodine Radioisotopes; D011945:Receptors, Angiotensin; D000804:Angiotensin II; D003900:Desoxycorticosterone; D000450:Aldosterone; C074793:angiotensin II, Sar(1)-; D007703:Peptidyl-Dipeptidase A