Glucagon-like peptide (GLP-1) is involved in the central modulation of fecal output in rats
Glucagon-like peptide (GLP-1) is involved in the central modulation of fecal output in rats
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DOI：
10.1152/ajpgi.2000.278.6.g924
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发表时间：
2000-06-01
影响因子：
4.5
通讯作者：
Yegen, BÇ
中科院分区：
文献类型：
--
作者：
Gülpinar, MA;Bozkurt, A;Yegen, BÇ
外源性应用胰高血糖素样肽(GLP-1)除了具有促胰岛素作用外，还通过中枢途径抑制胃胰腺的运动和分泌。本研究的目的是评估外源性GLP-1-(7-36)酰胺对粪便产量的影响，并探讨内源性GLP-1在应激诱导的结肠活动中的作用。成年雄性SD大鼠体重200~250g，采用立体定向仪，在氯胺酮麻醉下置入不锈钢脑室导管。一组大鼠被放置在Bollman式笼子中，以诱导束缚应激。侧脑室注射GLP-1可使监测2小时的大鼠粪便排泄量显著增加至500、1000和3000 pmol/只(P<；0.05~0.01)，而腹腔注射GLP-1则无明显影响。侧脑室注射GLP-1受体拮抗剂exendin-(9-39)(10nmol/鼠)可逆转GLP-1(500pmol/鼠；P<；0.01)引起的升高。注射促肾上腺皮质激素释放因子受体拮抗剂阿司匹林(10mUg/只，icv)也有类似的结果。侧脑室注射Exendin(10nmol/只大鼠)和Astressin(10mug/只大鼠；P<0.01-0.001)也能显著降低束缚应激引起的粪便小球产量的显著增加。这些结果表明，GLP-1通过其自身的受体参与结肠运动的中枢调节，而不是外周调节，GLP-1可能是一个候选的脑肠肽，作为应激诱导的结肠运动的生理调节器。
In addition to its insulinotropic action, exogenously administered glucagon-like peptide (GLP-1) inhibits gastropancreatic motility and secretion via central pathways. The aims of the present study were to evaluate the effects of exogenous GLP-1-(7-36) amide on fecal output and to investigate the role of endogenous GLP-1 on stress-induced colonic activity. With the use of a stereotaxic instrument, adult male Sprague-Dawley rats weighing 200-250 g were fitted with stainless steel cerebroventricular guide cannulas under ketamine anesthesia. A group of rats were placed in Bollman-type cages to induce restraint stress. Fecal output monitored for 2 h was increased significantly by intracerebroventricular GLP-1 to 500, 1,000, and 3,000 pmol/rat (P < 0.05-0.01), whereas intraperitoneal GLP-1 had no effect. Intracerebroventricular administration of the GLP-1 receptor antagonist exendin-(9-39) (10 nmol/rat) reversed the increases induced by GLP-1 (500 pmol/rat; P < 0.01). Similar results were also observed with the injection of corticotropin-releasing factor receptor antagonist astressin (10 mu g/rat icv). The significant increase in fecal pellet output induced by restraint stress was also decreased by both intracerebroventricular exendin (10 nmol/rat) and astressin (10 mu g/rat; P < 0.01-0.001). These results suggest that GLP-1 participates in the central, but not peripheral, regulation of colonic motility via its own receptor and that GLP-1 is likely to be a candidate brain-gut peptide that acts as a physiological modulator of stress-induced colonic motility.