Desensitization of Type 1 Angiotensin II Receptor Subtypes in the Rat Kidney

• Published in: Endocrinology (Philadelphia) 2001-11, Vol.142 (11), p.4683-4692
• Main Authors: Hus-Citharel, A, Bouby, N, Marchetti, J, Chansel, D, Goidin, D, Gourdji, D, Corvol, P, Llorens-Cortes, C
• Format: Article
• Language: English
• Subjects: Angiotensin AT1 receptors; Angiotensin II; Angiotensin II - pharmacology; Animals; Arterioles - metabolism; Biological effects; Calcium (intracellular); Calcium - metabolism; Cells, Cultured; Desensitization; Dose-Response Relationship, Drug; Glomerulus; Intracellular Membranes - metabolism; Kidney - metabolism; Kidney Glomerulus - cytology; Kidney Glomerulus - metabolism; Loop of Henle - cytology; Loop of Henle - metabolism; Male; mRNA; Osmolar Concentration; Pituitary (anterior); Pituitary Gland, Anterior - cytology; Pituitary Gland, Anterior - metabolism; Protein Kinase C - physiology; Rats; Rats, Sprague-Dawley; Receptor, Angiotensin, Type 1; Receptors; Receptors, Angiotensin - drug effects; Receptors, Angiotensin - metabolism; Sensory neurons
• ISSN: 0013-7227; 1945-7170
• DOI: 10.1210/endo.142.11.8485

Differences involving serine residues in the sequence of the carboxyl-terminal tail of type 1 angiotensin II (Ang II) receptor subtypes AT1A and AT1B suggest differences in desensitization ability. We examined the Ang II-induced homologous desensitization patterns of both receptor subtypes in freshly isolated renal structures: glomerulus (Glom), afferent arteriole, and cortical thick ascending limb (CTAL), whose content in each subtype mRNA is different, by measuring variations in intracellular calcium concentration. A preexposure to a maximal dose of Ang II, followed by a second application of the same concentration, induced: 1) a complete desensitization in Glom, where AT1A and AT1B mRNAs were expressed in similar proportions, and 2) no or partial desensitization in afferent arteriole and CTAL, where AT1A mRNA was predominant. In the absence of nephron structure containing only AT1B mRNA, we studied rat anterior pituitary cells that exhibit high content in this subtype and observed that desensitization was not complete. In Glom, CTAL, and pituitary cells, desensitization proceeded in a dose-dependent manner. In Glom and CTAL, desensitization occurred via a PKC-independent mechanism. These results suggest that desensitization does not depend on the nature of Ang II receptor subtype but either on the proportion of each subtype in a given cell and/or on cell specific type. This could allow adaptive biological responses to Ang II appropriate to the specific function of a given cell type.