Mommsen T P, Mojsov S
Department of Biochemistry and Microbiology, University of Victoria, BC, Canada.
Comp Biochem Physiol B Biochem Mol Biol. 1998 Sep;121(1):49-56. doi: 10.1016/s0305-0491(98)10110-4.
Glucagon-like peptide (GLP) exerts important physiological functions in fish liver, but extrahepatic sites of action and physiological roles have been largely ignored. We show here that GLP activates adenylyl cyclase in isolated brain and enterocyte membranes and increases cellular cyclic adenosine monophosphate (cAMP) levels in isolated enterocytes of rockfish (Sebastes caurinus). Following exposure to synthetic zebrafish GLP (zf-GLP) (1 nM-1 microM), a concentration-dependent increase in enterocyte cAMP is noted. The maximum increase in cAMP levels is observed at 1 microM zf-GLP, and represents a 30% increase above control values. Exendin-4, a GLP receptor agonist in mammals, elicits a similar concentration-dependent increase in enterocyte cAMP. In contrast, norepinephrine or prostaglandin E2 (at 1 microM) increased cAMP levels by 2 and 4-fold, respectively. Brain membrane adenylyl cyclase is activated 20-40% by zf-GLP, and to a smaller extent by zf-glucagon, while exendin-4 is as effective as zf-GLP at a dose of 100 nM. These results suggest potential physiological roles of GLP in brain and intestine in piscine systems analogous to GLP-1 functions in these tissues described for mammals.
胰高血糖素样肽（GLP）在鱼肝中发挥重要的生理功能，但肝外作用位点和生理作用在很大程度上被忽视了。我们在此表明，GLP可激活分离的脑和肠细胞膜中的腺苷酸环化酶，并提高岩鱼（Sebastes caurinus）分离肠细胞中的细胞环磷酸腺苷（cAMP）水平。在暴露于合成的斑马鱼GLP（zf-GLP）（1 nM - 1 microM）后，观察到肠细胞cAMP呈浓度依赖性增加。在1 microM zf-GLP时观察到cAMP水平的最大增加，比对照值增加了30%。艾塞那肽-4是哺乳动物中的一种GLP受体激动剂，它能引起肠细胞cAMP类似的浓度依赖性增加。相比之下，去甲肾上腺素或前列腺素E2（1 microM）分别使cAMP水平增加了2倍和4倍。zf-GLP可使脑膜腺苷酸环化酶激活20% - 40%，zf-胰高血糖素的激活程度较小，而在100 nM剂量下，艾塞那肽-4与zf-GLP的效果相同。这些结果表明，在鱼类系统中，GLP在脑和肠道中具有潜在的生理作用，类似于在哺乳动物中描述的这些组织中GLP-1的功能。
