Novel, Membrane-Intrinsic Receptors for Progesterone and Aldosterone

Abstract

In 1972, binding of [³H] aldosterone to plasma membranes from rat kidney with K_d ~ 100 nM was reported [1]. In a similar system, solubilization of binding activity was performed, but no further identification had been achieved [2]. Apart from these studies in the classical mineralocorticoid target organ, Armanini et al. [3] reported specific high-affinity binding of [³H] aldosterone to mononuclear leukocytes. The dissociation constant K_d was 2.7 nM with a binding site density of 209 sites per cell. The order of binding affinities was aldosterone ≈ deoxycorticosterone ≈ corticosterone > hydrocortisone > dexamethasone, which differs from the selectivity profile of the classic nuclear mineralocorticoid receptor (MR). Microsomal membranes from mononuclear leukocytes were subjected to photochemical crosslinking with the radioligand aldosterone-3-(0-carboxymethyl)-oximino-(2-[¹²⁵I]iodohistamine) in the presence and absence of an excess of unlabeled aldosterone. After SDS electrophoresis, a prominent maximum was visible at ~50 kDa which could be displaced by aldosterone, but not Cortisol [4]. Later, plasma membrane preparations from porcine kidney were studied with regard to non-classical receptors.