The natriuretic peptide (NP) family consists of cardiac NPs (ANP, BNP, and VNP) and brain NPs (CNPs) in teleosts. In addition to CNP1-4, a paralogue of CNP4 (named CNP4b) was recently discovered in basal teleosts including Japanese eel. Mammals have lost most Cnps during the evolution, but teleost cnps were conserved and diversified, suggesting that CNPs are important hormones for maintaining brain functions in teleost. The present study evaluated the potency of each Japanese eel CNP to their NP receptors (NPR-A, NPR-B, NPR-C, and NPR-D) overexpressed in CHO cells. A comprehensive brain map of cnps- and nprs-expressing neurons in Japanese eel was constructed by integrating the localization results obtained by in situ hybridization. The result showed that CHO cells expressing NPR-A and NPR-B induced strong cGMP productions after stimulation by cardiac and brain NPs, respectively. Regarding brain distribution of cnps, cnp1 is engaged in the ventral telencephalic area and periventricular area including the parvocellular preoptic nucleus (Pp), anterior/posterior tuberal nuclei, and periventricular gray zone of the optic tectum. cnp3 is found in the habenular nucleus and prolactin cells in the pituitary. cnp4 is expressed in the ventral telencephalic area, while cnp4b is expressed in the motoneurons in the medullary area. Such CNP isoform-specific localizations suggest that function of each CNP has diverged in the eel brain. Furthermore, the Pp lacking the blood-brain barrier expressed both npra and nprb, suggesting that endocrine and paracrine NPs interplay for regulating the Pp functions in Japanese eels.

硬骨鱼中的利钠肽 (NP) 家族由心脏 NP（ANP、BNP 和 VNP）和脑 NP (CNP) 组成。除了CNP1-4之外，最近在包括日本鳗鱼在内的基础硬骨鱼中还发现了CNP4的旁系同源物（称为CNP4b）。哺乳动物在进化过程中丢失了大部分CNPs ，但硬骨鱼的CNPs却得到了保存和多样化，这表明CNPs是硬骨鱼维持大脑功能的重要激素。本研究评估了每种日本鳗鱼 CNP 对其在 CHO 细胞中过表达的 NP 受体（NPR-A、NPR-B、NPR-C 和 NPR-D）的效力。通过整合原位杂交获得的定位结果，构建了日本鳗鱼表达cnp s 和npr s 的神经元的综合脑图。结果表明，表达 NPR-A 和 NPR-B 的 CHO 细胞分别在心脏和脑部 NP 刺激后诱导强烈的 cGMP 产生。关于cnp的脑分布，cnp1参与腹侧端脑区和脑室周围区域，包括小细胞视前核 (Pp)、前/后结节核和视顶盖的脑室周围灰区。cnp3存在于缰核和垂体催乳素细胞中。cnp4在腹侧端脑区表达，而cnp4b在髓质区的运动神经元中表达。这种 CNP 亚型特异性定位表明，每个 CNP 的功能在鳗鱼大脑中存在差异。此外，缺乏血脑屏障的 Pp 同时表达npra和nprb，这表明内分泌和旁分泌 NP 相互作用，调节日本鳗鱼的 Pp 功能。