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Initial studies of the receptor focused on the potential therapeutic ability for growth hormone (GH) release to reduce wasting in aging individuals, as well as food intake regulation for treatment of cachexia. Known roles of GHSR1a now extend to regulation of neurogenesis, learning and memory, gastrointestinal motility, glucose\/lipid metabolism, the cardiovascular system, neuronal protection, motivational salience, and hedonic feeding. Ghrelin, the endogenous agonist of GHSR1a, is primarily located in the stomach and is absent from the central nervous system (CNS), including the spinal cord. However, ghrelin in the circulation does have access to a small number of CNS sites, including the arcuate nucleus, which is important in feeding control. At some sites, such as at somatotrophs, GHSR1a has high constitutive activity. Typically, ghrelin\u2010dependent and constitutive GHSR1a activation occurs via G\u03b1\n                    <jats:sub>q\/11<\/jats:sub>\n                    pathways. In vitro and in vivo data suggest that GHSR1a heterodimerises with multiple G protein\u2010coupled receptors (GPCRs), including dopamine D1 and D2, serotonin 2C, orexin, oxytocin and melanocortin 3 receptors (MCR3), as well as the MCR3 accessory protein, MRAP2, providing possible mechanisms for its many physiological effects. In all cases, the receptor interaction changes downstream signalling and the responses to receptor agonists. This review discusses the signalling mechanisms of GHSR1a alone and in combination with other GPCRs, and explores the physiological consequences of GHSR1a coupling with other GPCRs.\n                  <\/jats:p>","DOI":"10.1111\/jne.13077","type":"journal-article","created":{"date-parts":[[2021,12,9]],"date-time":"2021-12-09T06:06:04Z","timestamp":1639029964000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["G protein\u2010coupled receptor interactions and modification of signalling involving the ghrelin receptor, GHSR1a"],"prefix":"10.1111","volume":"34","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7890-307X","authenticated-orcid":false,"given":"Mitchell Ty","family":"Ringuet","sequence":"first","affiliation":[{"name":"Department of Anatomy and Physiology University of Melbourne  Parkville VIC Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0219-3438","authenticated-orcid":false,"given":"John Barton","family":"Furness","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Physiology University of Melbourne  Parkville VIC Australia"},{"name":"Florey Institute of Neuroscience and Mental Health  Parkville VIC Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8655-8221","authenticated-orcid":false,"given":"Sebastian George Barton","family":"Furness","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences Faculty of Medicine The University of Queensland  St Lucia QLD Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,12,20]]},"reference":[{"key":"e_1_2_9_2_1","first-page":"287","volume-title":"Molecular endocrinology","author":"Bowers CY","year":"1977"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1210\/endo-114-5-1537"},{"key":"e_1_2_9_4_1","unstructured":"BowersC MomanyF ReynoldsG.In vitro and in vivo activity of a small synthetic peptide with potent GH releasing activity. Paper presented at: 64th Annual Meeting of the Endocrine Society San Francisco1982."},{"key":"e_1_2_9_5_1","unstructured":"BowersC MomanyF ReynoldsG SartorO.Multiple receptors mediate GH release. 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