{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T19:02:54Z","timestamp":1785351774081,"version":"3.55.0"},"reference-count":60,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2023,3,21]],"date-time":"2023-03-21T00:00:00Z","timestamp":1679356800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Neurogastroenterology Motil"],"published-print":{"date-parts":[[2023,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Electrical vagal stimulation alleviates abdominal surgery (AS)\u2010induced intestinal inflammation. Ghrelin receptors (GHS\u2010Rs) are expressed in the brain and peripheral tissues. We investigated the influence of HM01, an orally active ghrelin agonist crossing the blood\u2013brain barrier, on AS\u2010induced gastric inflammation and emptying (GE) in rats.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>HM01 (6\u00a0mg\/kg) or saline pretreatment was administered per orally (po) or intraperitoneally (ip). We assessed GE, gastric cytokine mRNA, and Fos positive cells in the dorsal motor nucleus of the vagus (DMN) and gastric corpus myenteric plexus (MP) in sham (anesthesia alone) and AS groups. The transcripts of GHS\u2010R1 variants were determined in the medulla oblongata and gastric corpus of na\u00efve rats.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key results<\/jats:title><jats:p>In vehicle pretreated rats, HM01 (ip) significantly increased the number of Fos immunoreactive cells in the MP and DMN in 55% and 52% of cholinergic neurons respectively. Hexamethonium did not modify HM01\u2010induced Fos expression in the DMN while reducing it in the MP by 2\u2010fold with values still significantly higher than that in control groups. AS upregulated gastric IL\u20101\u03b2 and TNF\u03b1 expression and inhibited GE by 66.6%. HM01 (po) abolished AS\u2010induced gastric ileus and increased cytokine expression and elevated IL\u201010 by 4.0\u2010fold versus vehicle\/sham. GHS\u2010R1a mRNA level was 5.4\u2010fold higher than the truncated GHS\u2010R1b isoform in the brain medulla and 40\u2010fold higher in the gastric submucosa\/muscle layers than in the mucosa.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and inference<\/jats:title><jats:p>Peripheral HM0 activates central vagal and myenteric cholinergic pathways that may influence both central and peripheral targets to prevent AS\u2010induced gastric inflammatory and ileus.<\/jats:p><\/jats:sec>","DOI":"10.1111\/nmo.14561","type":"journal-article","created":{"date-parts":[[2023,3,21]],"date-time":"2023-03-21T09:38:28Z","timestamp":1679391508000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["The ghrelin agonist, <scp>HM01<\/scp> activates central vagal and enteric cholinergic neurons and reverses gastric inflammatory and ileus responses in rats"],"prefix":"10.1111","volume":"35","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0067-510X","authenticated-orcid":false,"given":"Pu\u2010Qing","family":"Yuan","sequence":"first","affiliation":[{"name":"VA Greater Los Angeles Healthcare System  Los Angeles California USA"},{"name":"Vatche and Tamar Manoukian Division of Digestive Diseases Department of Medicine David Geffen School of Medicine CURE: Digestive Diseases Research Center (DDRC) Center for Neurobiology of Stress and Resilience (CNSR) University of California Los Angeles  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. 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