title: Cross talk between angiotensin AT1 and alpha 1-adrenergic receptors: angiotensin II downregulates alpha 1a-adrenergic receptor subtype mRNA and density in neonatal rat cardiac myocytes.
abstract: Signaling mediated by the angiotensin (Ang) II and alpha1-adrenergic receptor (alpha1-AR) pathways is important for cardiovascular homeostasis. However, it is unknown whether Ang II has any direct effect on alpha1-AR expression and signaling in cardiac myocytes. In the present study, we determined alpha1-AR subtype mRNA levels by RNase protection; receptor density by competition binding with 5-methylurapidil; and alpha1-AR-mediated c-fos expression by Northern blot analysis. We found that Ang II had no effect on alpha1b- and alpha1d-AR mRNA levels but decreased the alpha1a-AR mRNA level in a time- and dose-dependent manner. The maximal effect occurred at 6 hours with 100 nmol/L Ang II (40.0+/-8.2% reduction, n=4, P<.01). The decrease in alpha1a-AR mRNA level induced by Ang II is mediated by the Ang II AT1 receptor subtype and is associated with decreased stability of alpha1a-AR mRNA. Corresponding to the changes in the alpha1a-AR mRNA level, Ang II (100 nmol/L, 24 hours) reduced the density of high-affinity sites for 5-methylurapidil (alpha1A-AR) by 29% (56.5+/-6.4 versus 79.0+/-11.6 fmol/mg protein, n=4, P<.05). Alpha1-AR-stimulated c-fos induction, which could be blocked by 5-methylurapidil but not by chloroethylclonidine, was attenuated by Ang II preincubation (100 nmol/L, 24 hours). We conclude that there is previously undescribed cross talk between AT1 receptors and alpha1-ARs. Ang II selectively downregulates alpha1a-AR subtype mRNA and its corresponding receptor as well as alpha1a-AR-mediated expression of the immediate-early gene c-fos in cardiac myocytes.
authors.affiliation: Veterans Affairs Medical Center, the Cardiovascular Research Institute, and the Department of Medicine, University of California, San Francisco 94121, USA.
authors.forename: H T
authors.initials: HT
authors.lastname: Li
authors.forename: C S
authors.initials: CS
authors.lastname: Long
authors.forename: M O
authors.initials: MO
authors.lastname: Gray
authors.forename: D G
authors.initials: DG
authors.lastname: Rokosh
authors.forename: N Y
authors.initials: NY
authors.lastname: Honbo
authors.forename: J S
authors.initials: JS
authors.lastname: Karliner
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D015536:Down-Regulation / Q000187:drug effects; D016762:Genes, fos / Q000187:drug effects; D009206:Myocardium / Q000166:cytology / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D018340:Receptors, Adrenergic, alpha-1 / Q000235:genetics* / Q000378:metabolism*; D011945:Receptors, Angiotensin / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D018340:Receptors, Adrenergic, alpha-1; D011945:Receptors, Angiotensin; D000804:Angiotensin II