Brunetti Luigi, Orlando Giustino, Recinella Lucia, Leone Sheila, Ferrante Claudio, Chiavaroli Annalisa, Lazzarin Francesco, Vacca Michele
Department of Drug Sciences, G. d'Annunzio University, Chieti, Italy.
Peptides. 2008 Aug;29(8):1377-81. doi: 10.1016/j.peptides.2008.04.007. Epub 2008 Apr 20.
Glucagon-like peptide 1 (7-36) amide (GLP-1) and exendin-4 are gastrointestinal hormones as well as neuropeptides involved in glucose homeostasis and feeding regulation, both peripherally and at the central nervous system (CNS), acting through the same GLP-1 receptor. Aminergic neurotransmitters play a role in the modulation of feeding in the hypothalamus and we have previously found that peripheral hormones and neuropeptides, which are known to modulate feeding in the central nervous system, are able to modify catecholamine and serotonin release in the hypothalamus. In the present paper we have evaluated the effects of GLP-1 and exendin-4 on dopamine, norepinephrine, and serotonin release from rat hypothalamic synaptosomes, in vitro. We found that glucagon-like peptide 1 (7-36) amide and exendin-4 did not modify either basal or depolarization-induced dopamine and norepinephrine release; on the other hand glucagon-like peptide 1 (7-36) amide and exendin-4 stimulated serotonin release, in a dose dependent manner. We can conclude that the central anorectic effects of GLP-1 agonists could be partially mediated by increased serotonin release in the hypothalamus, leaving the catecholamine release unaffected.
胰高血糖素样肽1（7 - 36）酰胺（GLP - 1）和艾塞那肽-4是胃肠激素以及神经肽，它们参与外周和中枢神经系统（CNS）的葡萄糖稳态和进食调节，通过相同的GLP - 1受体发挥作用。胺能神经递质在下丘脑的进食调节中起作用，我们之前发现，已知能调节中枢神经系统进食的外周激素和神经肽能够改变下丘脑中儿茶酚胺和5-羟色胺的释放。在本文中，我们评估了GLP - 1和艾塞那肽-4对大鼠下丘脑突触体中多巴胺、去甲肾上腺素和5-羟色胺释放的体外影响。我们发现，胰高血糖素样肽1（7 - 36）酰胺和艾塞那肽-4既不改变基础状态下的，也不改变去极化诱导的多巴胺和去甲肾上腺素释放；另一方面，胰高血糖素样肽1（7 - 36）酰胺和艾塞那肽-4以剂量依赖的方式刺激5-羟色胺释放。我们可以得出结论，GLP - 1激动剂的中枢性厌食作用可能部分是由下丘脑中5-羟色胺释放增加介导的，而去甲肾上腺素的释放不受影响。
