{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,3]],"date-time":"2026-04-03T22:30:30Z","timestamp":1775255430363,"version":"3.50.1"},"reference-count":79,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2018,11,13]],"date-time":"2018-11-13T00:00:00Z","timestamp":1542067200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100009846","name":"Nova Southeastern University","doi-asserted-by":"publisher","award":["33932"],"award-info":[{"award-number":["33932"]}],"id":[{"id":"10.13039\/100009846","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Neurochemistry"],"published-print":{"date-parts":[[2019,1]]},"abstract":"Abstract<\/jats:title>\n \n \n \n \u03b2arrestin (\u03b2arr)\u20101 and \u20102 are ubiquitously (outside the retina) expressed G\u2010protein\u2010coupled receptor adapter proteins. They uncouple G\u2010protein\u2010coupled receptors from G proteins, internalize the receptor, and subsequently initiate their own wave of signaling independently of G proteins. Angiotensin (Ang)\n II<\/jats:styled-content>\n type 1 receptor (\n AT<\/jats:styled-content>\n 1<\/jats:sub>\n R) is a well\u2010established example of a receptor signaling through \u03b2arrs. Despite the pivotal role of brain\n AT<\/jats:styled-content>\n 1<\/jats:sub>\n Rs in the regulation of blood pressure, the involvement of \u03b2arr\u2010dependent signaling, mediated by\n AT<\/jats:styled-content>\n 1<\/jats:sub>\n Rs is not well studied. Particularly, in brain astrocytes very little is known about the effects of \u03b2arrs in\n AT<\/jats:styled-content>\n 1<\/jats:sub>\n R signaling. Herein, we utilized a combination of pharmacological and gene manipulation approaches to investigate the role of \u03b2arrs in\n AT<\/jats:styled-content>\n 1<\/jats:sub>\n R\u2010mediated signaling in isolated brainstem astrocytes from spontaneously hypertensive rats (\n SHR<\/jats:styled-content>\n s) and Wistar rats. We observed that \u03b2arr1 is the predominant arrestin isoform at the protein level in these cells. Its expression was down\u2010regulated in\n SHR<\/jats:styled-content>\n astrocytes compared to Wistar rat astrocytes. Ang\n II<\/jats:styled-content>\n , contrary to observations in\n SHR<\/jats:styled-content>\n astrocytes where it had no effect, up\u2010regulates \u03b2arr1 protein in Wistar rat astrocytes. We observed differential involvement of \u03b2arr1 in\n MAPK<\/jats:styled-content>\n activation in brainstem astrocytes of\n SHR<\/jats:styled-content>\n versus Wistar rats. The \u03b2arr\u2010biased agonist peptide [Sar\n 1<\/jats:sup>\n , Il\n 4<\/jats:sup>\n , Il8] Ang\u2010\n II<\/jats:styled-content>\n (\n SII<\/jats:styled-content>\n ), induced\n AT<\/jats:styled-content>\n 1<\/jats:sub>\n R\u2010mediated\n ERK<\/jats:styled-content>\n and p38 activation in Wistar rat astrocytes.\n SII<\/jats:styled-content>\n had no effect on\n ERK<\/jats:styled-content>\n and p38 activation in\n SHR<\/jats:styled-content>\n s brainstem astrocytes. Our results indicate, reduced involvement of \u03b2arr1 in dampening Ang\n II<\/jats:styled-content>\n \u2010induced\n MAPK<\/jats:styled-content>\n s activation and diminished \u03b2arr1\u2010mediated\n ERK<\/jats:styled-content>\n and p38 activation in\n SHR<\/jats:styled-content>\n brainstem astrocytes. These findings might be mechanistically related to the development of the brain renin\u2013angiotensin\u2013aldosterone system hyperactivity, which leads to pathogenesis of the hypertensive state of the\n SHR<\/jats:styled-content>\n model.\n <\/jats:p>\n <\/jats:sec>\n \n \n \n \n \n image<\/jats:alt-text>\n <\/jats:graphic>\n <\/jats:boxed-text>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/jnc.14620","type":"journal-article","created":{"date-parts":[[2018,10,22]],"date-time":"2018-10-22T18:51:04Z","timestamp":1540234264000},"page":"46-62","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Role of \u03b2arrestin1 in\n AT<\/scp>\n 1<\/sub>\n R\u2010mediated mitogen\u2010activated protein kinase activation in Wistar and\n SHR<\/scp>\n brainstem astrocytes"],"prefix":"10.1111","volume":"148","author":[{"given":"Shmuel","family":"Negussie","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Sciences College of Pharmacy Nova Southeastern University Fort Lauderdale Florida USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anastasios","family":"Lymperopoulos","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences College of Pharmacy Nova Southeastern University Fort Lauderdale Florida USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9262-0845","authenticated-orcid":false,"given":"Michelle A.","family":"Clark","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences College of Pharmacy Nova Southeastern University Fort Lauderdale Florida USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2018,11,13]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.C300443200"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.0000218576.36574.54"},{"key":"e_1_2_7_4_1","doi-asserted-by":"crossref","first-page":"13","DOI":"10.36253\/ijae-1052","article-title":"Spontaneously hypertensive rat neuroanatomy: applications to pharmacological research","volume":"115","author":"Amenta F.","year":"2010","journal-title":"Ital. 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