title: Effects of centrally injected glucagon-like peptide-2 on gastric mucosal blood flow in rats: possible mechanisms.
abstract: "Glucagon-like peptide-2" (GLP-2) is a peptide that is released from the enteroendocrine L cells in response to food in the gastrointestinal tract. Peripheral injection of GLP-2 has been shown to increase gastrointestinal blood flow, but effects of central GLP-2 on any vascular bed has not been studied yet. The aim of this study is to investigate the effects of various doses of intracerebroventricularly (i.c.v.)-injected GLP-2 on gastric mucosal blood flow (GMBF) and contribution of calcitonin gene related peptide (CGRP), nitric oxide synthase-nitric oxide (NOS-NO) and cyclooxygenase-prostaglandin (COX-PG) systems to the possible effect. The gastric chamber technique was used to determine GMBF. Urethane anesthesia was used throughout the recording procedure. Male Wistar rats were treated with GLP-2 (100, 150 ve 200ng/10μl; i.c.v.) or saline (10μl; i.c.v.) in order to find out the effective dose of i.c.v. GLP-2 on GMBF. Then, CGRP receptor antagonist CGRP-(8-37) (10μg/kg; s.c.), NOS inhibitor NG-nitro-l-arginine methyl ester (l-NAME; 30mg/kg; s.c.) or COX inhibitor indomethacin (5mg/kg; i.p.) was injected before the effective dose of i.c.v. GLP-2. GMBF was measured continuously for 35min following GLP-2 and recorded every fifth minute. Non-parametric Kruskal-Wallis test was used for statistical analysis. Differences were considered to be significant at p<0.05. GMBF increased rapidly following 100ng GLP-2 injection and did not fall to the basal levels during 35min. Other doses of i.c.v. GLP-2 did not produce any significant difference in GMBF. CGRP receptor antagonist, CGRP-(8-37) (10μg/kg; s.c.) and COX inhibitor indomethacin (5mg/kg; i.p.) significantly prevented the increase in GMBF due to GLP-2 (100ng; i.c.v.), while l-NAME (30mg/kg; s.c.) was ineffective. None of the drugs produced a significant change in GMBF when administered alone. Thus we suggest that, i.c.v. GLP-2 increases GMBF and CGRP and endogenous prostaglandins but not NO, contribute to this effect.
authors.affiliation: Acibadem University, School of Medicine, Department of Physiology, Istanbul, Turkey. Electronic address: guldal.suyen@acibadem.edu.tr.
authors.forename: Guldal
authors.initials: G
authors.lastname: Gulec Suyen
authors.affiliation: Uludağ University, School of Medicine, Department of Physiology, Bursa, Turkey.
authors.forename: Naciye
authors.initials: N
authors.lastname: Isbil-Buyukcoskun
authors.affiliation: Uludağ University, School of Medicine, Department of Physiology, Bursa, Turkey.
authors.forename: Betul
authors.initials: B
authors.lastname: Cam
authors.affiliation: Uludağ University, School of Medicine, Department of Physiology, Bursa, Turkey.
authors.forename: Kasim
authors.initials: K
authors.lastname: Ozluk
mesh_terms: D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000187:drug effects; D005753:Gastric Mucosa / Q000098:blood supply* / Q000187:drug effects; D053767:Glucagon-Like Peptide 2 / Q000008:administration & dosage*; D057967:Infusions, Intraventricular; D008297:Male; D019001:Nitric Oxide Synthase / Q000187:drug effects; D011451:Prostaglandin-Endoperoxide Synthases / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D012039:Regional Blood Flow / Q000187:drug effects
chemical_list: D053767:Glucagon-Like Peptide 2; D019001:Nitric Oxide Synthase; D011451:Prostaglandin-Endoperoxide Synthases; D015740:Calcitonin Gene-Related Peptide
keywords: CGRP-(8-37); Gastric mucosal blood flow; Glucagon like peptide-2; Indomethacin; l-NAME