The hypocretins: Hypothalamus-specific peptides with neuroexcitatory activity

We describe a hypothalamus-specific mRNA that encodes preprohypocretin, the putative precursor of a pair of peptides that share substantial amino acid identities with the gut hormone secretin. The hypocretin (Hcrt) protein products are restricted to neuronal cell bodies of the dorsal and lateral hypothalamic areas. The fibers of these neurons are widespread throughout the posterior hypothalamus and project to multiple targets in other areas, including brainstem and thalamus. Hcrt immunoreactivity is associated with large granular vesicles at synapses. One of the Hcrt peptides was excitatory when applied to cultured, synaptically coupled hypothalamic neurons, but not hippocampal neurons. These observations suggest that the hypocretins function within the CNS as neurotransmitters.

我们报道了一种下丘脑特异性信使核糖核酸（mRNA），其编码前下丘脑泌素原（preprohypocretin）——该蛋白是一对与肠道激素促胰液素（secretin）具有高度氨基酸同源性的肽类的推定前体。下丘脑泌素（hypocretin，以下简称Hcrt）的蛋白产物仅局限于背侧下丘脑区与外侧下丘脑区的神经元胞体中。这类神经元的神经纤维广泛分布于整个下丘脑后部，并向脑干、丘脑等其他脑区的多个靶位点投射。Hcrt免疫反应活性与突触处的大型颗粒囊泡相关联。将其中一种Hcrt肽类施加于体外培养的、突触连接的下丘脑神经元时可引发兴奋性反应，但对海马神经元无此效应。上述观察结果表明，下丘脑泌素在中枢神经系统（CNS）中作为神经递质发挥功能。