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Selective antagonism of mitogen‐activated protein (MAP) kinase ‐, but not phospholipase C (PLC)‐, dependent angiotensin II (Ang II) actions in brain
Author(s) -
Yosten Gina L.C.,
Liu Jun,
Sandberg Kathryn,
Samson Willis K.
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.936.2
Subject(s) - angiotensin ii , endocrinology , protein kinase c , medicine , protein kinase a , mapk/erk pathway , kinase , renin–angiotensin system , mitogen activated protein kinase , biology , chemistry , signal transduction , receptor , microbiology and biotechnology , blood pressure
Hallmark central nervous system actions of Ang II include stimulation of ingestive behaviors and activation of the autonomic nervous system. We identified a 7 amino acid peptide (PEP7) encoded within a short open reading frame in exon 2 of the rat angiotensin type 1a receptor (AT1aR) gene that inhibits Ang II‐induced activation of extracellular–regulated kinase 1&2 (ERK1/2), suggesting that PEP7 inhibits AT1aR action. We investigated the potential for PEP7 to antagonize the central actions of Ang II. Central administration of 1 nmole PEP7 significantly abrogated ingestion of 1.5% NaCl, but not water, in response to a stimulatory dose of Ang II (25 pmole) in male rats. Since saline drinking in response to Ang II is dependent upon the MAP‐kinase pathway, while water ingestion is activated by a protein kinase C (PKC)‐dependent pathway (Daniels et al. Exp Physiol 94:130,2008), these results suggest that PEP7 is a selective antagonist of MAP‐kinase‐dependent actions of Ang II. PEP7 pretreatment did not alter water drinking in response to overnight water restriction or the central autonomic actions of Ang II, suggesting that in those models, the actions of Ang II are more dependent upon PKC signaling than the ERK1/2 pathway. Thus PEP7 may be an important tool with which the solute‐dependent actions of Ang II can be isolated from those related to volume homeostasis. [NIH 066023 (WKS), NIH HL‐57502 (KS)]