Gulec Suyen Guldal, Isbil-Buyukcoskun Naciye, Cam Betul, Ozluk Kasim
Acibadem University, School of Medicine, Department of Physiology, Istanbul, Turkey.
Uludağ University, School of Medicine, Department of Physiology, Bursa, Turkey.
Peptides. 2015 Feb;64:62-6. doi: 10.1016/j.peptides.2014.12.008. Epub 2015 Jan 13.
"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.
“胰高血糖素样肽 -2”（GLP -2）是一种肽类物质，它由肠道内分泌L细胞在胃肠道内有食物时释放。已表明外周注射GLP -2可增加胃肠道血流量，但中枢GLP -2对任何血管床的影响尚未得到研究。本研究的目的是调查不同剂量脑室内（i.c.v.）注射GLP -2对胃黏膜血流量（GMBF）的影响，以及降钙素基因相关肽（CGRP）、一氧化氮合酶 - 一氧化氮（NOS - NO）和环氧化酶 - 前列腺素（COX - PG）系统对这种可能影响的贡献。采用胃腔技术测定GMBF。在整个记录过程中使用乌拉坦麻醉。为了找出i.c.v. GLP -2对GMBF的有效剂量，给雄性Wistar大鼠注射GLP -2（100、150和200 ng/10μl；i.c.v.）或生理盐水（10μl；i.c.v.）。然后，在注射有效剂量的i.c.v. GLP -2之前，注射CGRP受体拮抗剂CGRP -（8 - 37）（10μg/kg；皮下注射）、NOS抑制剂NG - 硝基 - L - 精氨酸甲酯（L - NAME；30mg/kg；皮下注射）或COX抑制剂吲哚美辛（5mg/kg；腹腔注射）。在注射GLP -2后连续35分钟测量GMBF，并每隔5分钟记录一次。采用非参数Kruskal - Wallis检验进行统计分析。当p<0.05时，差异被认为具有统计学意义。注射100 ng GLP -2后GMBF迅速增加，并且在35分钟内未降至基础水平。其他剂量的i.c.v. GLP -2在GMBF方面未产生任何显著差异。CGRP受体拮抗剂CGRP -（8 - 37）（10μg/kg；皮下注射）和COX抑制剂吲哚美辛（5mg/kg；腹腔注射）显著抑制了由于GLP -2（100 ng；i.c.v.）引起的GMBF增加，而L - NAME（30mg/kg；皮下注射）无效。单独给药时，这些药物均未使GMBF产生显著变化。因此，我们认为，i.c.v. GLP -2增加GMBF，并且CGRP和内源性前列腺素而非NO促成了这种作用。
