Regulation of nonclassical renin-angiotensin system receptor gene expression in the adrenal medulla by acute and repeated immobilization stress

Am J Physiol Regul Integr Comp Physiol. 2015 Mar 15;308(6):R517-29. doi: 10.1152/ajpregu.00130.2014. Epub 2015 Jan 14.

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.

Keywords: (pro)renin receptor; Mas receptor; angiotensin II type 4 receptor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenal Medulla / metabolism*
  • Adrenal Medulla / physiopathology
  • Animals
  • Catecholamines / biosynthesis
  • Disease Models, Animal
  • Gene Expression Regulation
  • Immobilization*
  • Male
  • Mitogen-Activated Protein Kinase 1 / metabolism
  • Mitogen-Activated Protein Kinase 3 / metabolism
  • PC12 Cells
  • Phosphorylation
  • Proto-Oncogene Mas
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism
  • Proton-Translocating ATPases / genetics
  • Proton-Translocating ATPases / metabolism
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, Angiotensin, Type 2 / genetics
  • Receptor, Angiotensin, Type 2 / metabolism
  • Receptors, Angiotensin / genetics
  • Receptors, Angiotensin / metabolism
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / metabolism
  • Receptors, G-Protein-Coupled / genetics
  • Receptors, G-Protein-Coupled / metabolism
  • Renin-Angiotensin System* / genetics
  • Serine
  • Stress, Psychological / genetics
  • Stress, Psychological / metabolism*
  • Stress, Psychological / physiopathology
  • Time Factors
  • Tyrosine 3-Monooxygenase / metabolism
  • Vacuolar Proton-Translocating ATPases

Substances

  • AT4 receptor
  • Catecholamines
  • Proto-Oncogene Mas
  • Proto-Oncogene Proteins
  • RNA, Messenger
  • Receptor, Angiotensin, Type 2
  • Receptors, Angiotensin
  • Receptors, Cell Surface
  • Receptors, G-Protein-Coupled
  • Serine
  • Tyrosine 3-Monooxygenase
  • Mapk1 protein, rat
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • ATP6AP2 protein, rat
  • Vacuolar Proton-Translocating ATPases
  • Proton-Translocating ATPases