Angiotensin II receptor heterogeneity

Journal Article · Mon Apr 01 04:00:00 EST 1991 · American Journal of Hypertension; (United States)

OSTI ID:5229566

Herblin, W F; Chiu, A T; McCall, D E; Ardecky, R J; Carini, D J; Duncia, J V; Pease, L J; Wong, P C; Wexler, R R; Johnson, A L ^[1]

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1. DuPont Merck Pharmaceutical Company, Wilmington, DE (USA)

The possibility of receptor heterogeneity in the angiotensin II (AII) system has been suggested previously, based on differences in Kd values or sensitivity to thiol reagents. One of the authors earliest indications was the frequent observation of incomplete inhibition of the binding of AII to adrenal cortical membranes. Autoradiographic studies demonstrated that all of the labeling of the rat adrenal was blocked by unlabeled AII or saralasin, but not by DuP 753. The predominant receptor in the rat adrenal cortex (80%) is sensitive to dithiothreitol (DTT) and DuP 753, and is designated AII-1. The residual sites in the adrenal cortex and almost all of the sites in the rat adrenal medulla are insensitive to both DTT and DuP 753, but were blocked by EXP655. These sites have been confirmed by ligand binding studies and are designated AII-2. The rabbit adrenal cortex is unique in yielding a nonuniform distribution of AII-2 sites around the outer layer of glomerulosa cells. In the rabbit kidney, the sites on the glomeruli are AII-1, but the sites on the kidney capsule are AII-2. Angiotensin III appears to have a higher affinity for AII-2 sites since it inhibits the binding to the rabbit kidney capsule but not the glomeruli. Elucidation of the distribution and function of these diverse sites should permit the development of more selective and specific therapeutic strategies.

• OSTI ID: 5229566
• Journal Information: American Journal of Hypertension; (United States), Journal Name: American Journal of Hypertension; (United States) Vol. 4:4 Pt 2; ISSN AJHYE; ISSN 0895-7061
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ADRENAL GLANDS
AFFINITY
ANGIOTENSIN
ANIMALS
AUTORADIOGRAPHY
BIOCHEMICAL REACTION KINETICS
BODY
CARDIOVASCULAR AGENTS
CELL CONSTITUENTS
CELL MEMBRANES
DISTRIBUTION
DRUGS
ENDOCRINE GLANDS
GLANDS
GLOBULINS
IODINE ISOTOPES
ISOTOPES
KIDNEYS
KINETICS
MAMMALS
MEMBRANE PROTEINS
MEMBRANES
MICROSOMES
ORGANIC COMPOUNDS
ORGANS
PROTEINS
RABBITS
RATS
REACTION KINETICS
RECEPTORS
RIBOSOMES
RODENTS
TISSUE DISTRIBUTION
VASOCONSTRICTORS
VERTEBRATES