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Blocking these receptors is part of the basis for \u03b2-blocker therapy for heart failure. Recent data demonstrate that G protein-coupled receptors (GPCRs), including \u03b2ARs, are activated intracellularly, although the biological significance is unclear. Here we investigated the functional role of Golgi \u03b2ARs in rat cardiac myocytes and found they activate Golgi localized, prohypertrophic, phosphoinositide hydrolysis, that is not accessed by cell surface \u03b2AR stimulation. This pathway is accessed by the physiological neurotransmitter norepinephrine (NE) via an Oct3 organic cation transporter. Blockade of Oct3 or specific blockade of Golgi resident \u03b21ARs prevents NE dependent cardiac myocyte hypertrophy. This clearly defines a pathway activated by internal GPCRs in a biologically relevant cell type and has implications for development of more efficacious \u03b2-blocker therapies.<\/jats:p>","DOI":"10.7554\/elife.48167","type":"journal-article","created":{"date-parts":[[2019,8,21]],"date-time":"2019-08-21T08:00:36Z","timestamp":1566374436000},"source":"Crossref","is-referenced-by-count":122,"title":["Golgi localized \u03b21-adrenergic receptors stimulate Golgi PI4P hydrolysis by PLC\u03b5 to regulate cardiac hypertrophy"],"prefix":"10.7554","volume":"8","author":[{"given":"Craig A","family":"Nash","sequence":"first","affiliation":[{"name":"Department of Pharmacology, University of Michigan School of Medicine, Ann Arbor, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenhui","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, University of Michigan School of Medicine, Ann Arbor, United 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