title: Regulation of nonclassical renin-angiotensin system receptor gene expression in the adrenal medulla by acute and repeated immobilization stress.
abstract: The involvement of the nonclassical renin-angiotensin system (RAS) in the adrenomedullary response to stress is unclear. Therefore, we examined basal and immobilization stress (IMO)-triggered changes in gene expression of the classical and nonclassical RAS receptors in the rat adrenal medulla, specifically the angiotensin II type 2 (AT2) and type 4 (AT4) receptors, (pro)renin receptor [(P)RR], and Mas receptor (MasR). All RAS receptors were identified, with AT2 receptor mRNA levels being the most abundant, followed by the (P)RR, AT1A receptor, AT4 receptor, and MasR. Following a single IMO, AT2 and AT4 receptor mRNA levels decreased by 90 and 50%, respectively. Their mRNA levels were also transiently decreased by repeated IMO. MasR mRNA levels displayed a 75% transient decrease as well. Conversely, (P)RR mRNA levels were increased by 50% following single or repeated IMO. Because of its abundance, the function of the (P)RR was explored in PC-12 cells. Prorenin activation of the (P)RR increased phosphorylation of extracellular signal-regulated kinase 1/2 and tyrosine hydroxylase at Ser(31), likely increasing its enzymatic activity and catecholamine biosynthesis. Together, the broad and dynamic changes in gene expression of the nonclassical RAS receptors implicate their role in the intricate response of the adrenomedullary catecholaminergic system to stress.
authors.affiliation: Department of Biochemistry and Molecular Biology, New York Medical College, Valhalla, New York.
authors.forename: Regina
authors.initials: R
authors.lastname: Nostramo
authors.affiliation: Department of Biochemistry and Molecular Biology, New York Medical College, Valhalla, New York.
authors.forename: Lidia
authors.initials: L
authors.lastname: Serova
authors.affiliation: Department of Biochemistry and Molecular Biology, New York Medical College, Valhalla, New York.
authors.forename: Marcela
authors.initials: M
authors.lastname: Laukova
authors.affiliation: Department of Biochemistry and Molecular Biology, New York Medical College, Valhalla, New York.
authors.forename: Andrej
authors.initials: A
authors.lastname: Tillinger
authors.affiliation: Department of Biochemistry and Molecular Biology, New York Medical College, Valhalla, New York.
authors.forename: Chandana
authors.initials: C
authors.lastname: Peddu
authors.affiliation: Department of Biochemistry and Molecular Biology, New York Medical College, Valhalla, New York esther_sabban@nymc.edu.
authors.forename: Esther L
authors.initials: EL
authors.lastname: Sabban
mesh_terms: D000313:Adrenal Medulla / Q000378:metabolism* / Q000503:physiopathology; D000818:Animals; D002395:Catecholamines / Q000096:biosynthesis; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D007103:Immobilization; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D016716:PC12 Cells; D010766:Phosphorylation; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D006180:Proton-Translocating ATPases / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D044139:Receptor, Angiotensin, Type 2 / Q000235:genetics / Q000378:metabolism; D011945:Receptors, Angiotensin / Q000235:genetics / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000235:genetics; D012694:Serine; D013315:Stress, Psychological / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D013997:Time Factors; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D025262:Vacuolar Proton-Translocating ATPases; D000093342:Prorenin Receptor
chemical_list: D002395:Catecholamines; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D006180:Proton-Translocating ATPases; D012333:RNA, Messenger; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D012694:Serine; D014446:Tyrosine 3-Monooxygenase; D025262:Vacuolar Proton-Translocating ATPases; C090830:AT4 receptor; C535149:Mapk1 protein, rat; C514240:ATP6AP2 protein, rat; D000093342:Prorenin Receptor
keywords: (pro)renin receptor; Mas receptor; angiotensin II type 4 receptor