By Tadashi Inagami, Masato Mizukoshi, Deng-Fu Guo (auth.), Juan M. Saavedra, Pieter B. M. W. M. Timmermans (eds.)
From molecular biology to medical purposes of selective receptor blockade, the current quantity compiles the most recent advances of this rising box. Of specific value is the eye given to the newly chanced on AT2 receptors, and the body structure and pathophysiology of angiotensin receptor subtypes. The publication will offer clinicians treating heart problems and high blood pressure with a clearer figuring out of this therapeutically very important and complex hormone.
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Extra info for Angiotensin Receptors
The open reading frame (black box) is included in exon 3. 5 ~ promoter teOoon . zN~ ~ :- tb (1) ...... ll(1)- ~ a. ~ ~ N Molecular Biology of ANG 11 Receptors 25 6. STRUCTURE-ACTIVITY RELATIONSHIP OF THE AT1 RECEPTOR To date, two studies designed to determine which amino acids are critical to the normal functioning of the AT I protein describe site-directed mutagenesis of the cDNA expressed transiently in COS-7 cells. The first report concentrated on mutations that may affect ANG II binding. 55 The replacement of any of the four cysteine residues from the extracellular domains by glycine markedly decreased affinity for [125I]-ANG II.
6. Coupling. to Other Ion Channels ANG IT can inhibit potassium channels, possibly through a G_protein. 136-138 The resulting depolarization may be involved in determining the level of cellular activation. ANG II may also depolarize cells through the opening of sodium channels, secondary to protein kinase C activation. 7. Temporal Sequence of Signaling Events: Example of Smooth Muscle The signaling sequence in smooth muscle is similar to that of adrenal granulosa or glomerular mesangial cells. These biochemical events were ini- Molecular Biology of ANG /I Receptors 35 tially studied in cultured vascular smooth muscle cells labeled with radioactive phospholipid precursors.
However, only type A coupled to protein synthesis. In view of the results described in this and previous sections, it appears that ANG II receptors of mesangial cells may be unique. Definitive classification will require cloning of these receptor subtypes. 11. NON-AT1 AND NON-AT2 ANG /I BINDING SITES Different authors have described ANG II binding sites that are not blocked by ATJ or AT2 antagonists. The data are still too recent to determine whether these sites correspond to a single new receptor.