Mineralocorticoid (type I) receptors in the olfactory mucosa of the mammal: studies with [3H]aldosterone and the anti-mineralocorticoid spironolactone.
High-affinity, specific binding sites to mineralocorticoids, with characteristics of mineralocorticoid (type I) receptors, have been found in the mammalian olfactory mucosa. In the presence of RU 28362, which blocks low-affinity binding of the labeled hormone to glucocorticoid (type II) receptors, Scatchard analysis of the specific [3H]aldosterone binding indicates that aldosterone binds to a single class of high-affinity (type I) sites with a dissociation constant, Kd, of 1.2 x 10(-9) M and a maximum number of binding sites, Bmax, of 63 fmol/mg dry tissue. Time course of association of [3H]aldosterone and its binding sites showed maximal binding by 30 min at 25 degrees C which remained unchanged up to 90 min. Competition studies performed with 1 x 10(-7)-1 x 10(-5) M spironolactone, a competitive mineralocorticoid antagonist, showed a dose-response reduction of [3H]aldosterone binding, implying that in the olfactory mucosa this compound behaves as an aldosterone antagonist. These results demonstrate significant [3H]aldosterone binding to receptors of high affinity and mineralocorticoid specificity and suggest that the olfactory mucosa is a target site for mineralocorticoid action.
Kern
R C
RC
Department of Otolaryngology-Head and Neck Surgery, Northwestern University, Chicago, IL, USA.
Foster
J D
JD
Pitovski
D Z
DZ
D000450:Aldosterone / Q000378:metabolism*; D000818:Animals; D001667:Binding, Competitive; D002250:Carbon Radioisotopes; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D007553:Isotope Labeling; D008297:Male; D000451:Mineralocorticoid Receptor Antagonists / Q000378:metabolism*; D009831:Olfactory Mucosa / Q000378:metabolism*; D018161:Receptors, Mineralocorticoid / Q000378:metabolism*; D013148:Spironolactone / Q000378:metabolism*; D014316:Tritium
D002250:Carbon Radioisotopes; D000451:Mineralocorticoid Receptor Antagonists; D018161:Receptors, Mineralocorticoid; D014316:Tritium; D013148:Spironolactone; D000450:Aldosterone