Corticosterone's metabolite is an agonist for Na sup + transport stimulation in A6 cells

Journal Article · Sat Oct 01 04:00:00 EDT 1988 · American Journal of Physiology; (USA)

OSTI ID:6036756

Duncan, R L; Grogan, W M; Kramer, L B; Watlington, C O ^[1]

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1. Virginia Commonwealth Univ., Richmond (USA)

This study tests the hypothesis, in A6 epithelia, that (1) corticosterone stimulates active Na{sup +} transport by an additional receptor mechanism to the type I (mineralocorticoid) and type II (glucocorticoid) mechanisms shared with aldosterone (Aldo) and (2) that the agonist may be 6{beta}-OH-corticosterone made in the effector cell. The dose-response relationship of corticosterone at 24 h resolves into two components, by curve fitting. The EC{sub 50} of the smaller component correlates with the apparent dissociation constant (K{prime}{sub d}) of corticosterone for high affinity (type II) nuclear binding sites shared with Aldo. In unlabeled analogue competition studies Aldo and corticosterone displaced nuclear binding equally below 10{sup {minus}8} M ({sup 3}H)corticosterone, indicating only shared sites. However, nonshared saturable sites were found at ({sup 3}H)corticosterone concentrations above 10{sup {minus}8} M. Concentration-binding curves performed with ({sup 3}H)corticosterone, in presence of 1,000 {times} Aldo to displace shared sites, revealed a single class of binding sites with a half-maximal saturation of 2 {times} 10{sup {minus}7} M, which is quite similar to the EC{sub 50} of the lower affinity component of I{sub sc} stimulation by corticosterone at 24 h. Reversed phase high-pressure liquid chromatography of nuclear extracts indicates that the saturable component of bound ({sup 3}H) was 6{beta}-OH-({sup 3}H)corticosterone derived from ({sup 3}H)corticosterone. Thus, A6 cells metabolize corticosterone to 6{beta}-OH-corticosterone, which in turn occupies lower-affinity receptors not shared with Aldo or corticosterone, to mediate most of the active Na{sup +} transport stimulation by corticosterone.

• OSTI ID: 6036756
• Journal Information: American Journal of Physiology; (USA), Journal Name: American Journal of Physiology; (USA) Vol. 255:4; ISSN 0002-9513; ISSN AJPHA
• Country of Publication: United States
• Language: English

Related Subjects

551001* -- Physiological Systems-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ADRENAL HORMONES
ALKALI METAL COMPOUNDS
ANIMAL TISSUES
BIOLOGICAL EFFECTS
BODY
CATIONS
CHARGED PARTICLES
CORTICOSTEROIDS
CORTICOSTERONE
DOSE-RESPONSE RELATIONSHIPS
EPITHELIUM
GLUCOCORTICOIDS
HYDROGEN COMPOUNDS
HYDROXY COMPOUNDS
IONS
ISOTOPE APPLICATIONS
KETONES
MEMBRANE TRANSPORT
METABOLITES
ORGANIC COMPOUNDS
PREGNANES
SODIUM COMPOUNDS
STEROIDS
TISSUES
TRACER TECHNIQUES
TRITIUM COMPOUNDS