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Endocrinology, doi:10.1210/endo-129-2-1075
Endocrinology Vol. 129, No. 2 1075-1082
Copyright © 1991 by the Endocrine Society.
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Angiotensin-II Receptor Subtypes in Fetal Tissues of the Rat: Autoradiography, Guanine Nucleotide Sensitivity, and Association with Phosphoinositide Hydrolysis

KEISUKE TSUTSUMI, CHRISTER STRÖMBERG, MOHAN VISWANATHAN and JUAN M. SAAVEDRA

Section on Pharmacology, Laboratory of Clinical Science, National Institute of Mental Health Bethesda, Maryland 20892

Address all correspondence and requests for reprints to: Dr. Keisuke Tsutsumi, Section on Pharmacology, Laboratory of Clinical Science, National Institute of Mental Health, 9000 Rockville Pike, Building 10, Room 2D-45, Bethesda, Maryland 20892.

Abstract

Quantitative autoradiography revealed large numbers of angiotensin-II (AT) receptors in the 18-day-old rat embryo. The selective AT-1 antagonist DuP 753 readily competed for AT receptors in liver, lung parenchyma, and choroid plexus, and these receptors are classified as AT-1 receptors. The selective AT-2 displacers CGP 42112 A and/or PD 123177 competed with high affinity with AT bound to most receptors located in skeletal muscle, skin, diaphragm, bronchi, and stomach, and these receptors are classified as AT-2 receptors. The amount of AT-2 receptors in fetal tissues was more than 10-fold higher than that of AT-1 receptors. In skeletal muscle and skin, DuP 753 competed with AT in the presence of 107 M CGP 42112 A, indicating the presence of small numbers of AT-1 receptors. In liver and lung parenchyma, binding to AT-1 receptors was sensitive to guanine nucleotides. AT binding to AT-2 receptors in fetal skin and skeletal muscle was insensitive to guanine nucleotides. AT stimulated phosphoinositide hydrolysis in liver (ED50) 64 nM) and in skin and skeletal muscle (ED60, 62 nM); this was inhibited by DuP 753 (liver IC50, 38 nM; skin and skeletal muscle IC50, 26 nM), but not by PD 123177 in concentrations up to the micromolar range. AT-1 receptors are probably coupled to G-proteins, and their stimulation increases phos-phoinositide hydrolysis. AT-2 receptors may not be linked to G-proteins, their stimulation is not associated with phosphoinositide hydrolysis, and the nature of their second messenger system(s) is presently unknown.

Received March 8, 1991.




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