Comparative molecular biology of the natriuretic peptide system (Molecular dissection and mechanism of differentiation of chloride cells)

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We used the comparative approach to gain insights into the complex regulatory system of the body fluid homeostasis by using animals with morphological and functional specializations such as the eel that can survive both in freshwater and seawater and the Osorezan dace that can live and grow in a pH 3.5 lake. (1) Through the analyses of both ligands and the corresponding receptors, we showed that the natriuretic peptide (NP) system is a key endocrine system that governs the euryhalinity of eel. NP is not only involved in quick regulation of various pre-existing transporters upon transfer to different salinities, but also stimulates secretion of cortisol and growth hormone, thereby being involved in long-term adaptation. We also identified NPs from diverse vertebrate species that perform unique osmoregulation such as sharks and hagfish to assess molecular evolution of the NP family. (2) Molecular mechanism of acid adaptation of the Osorezan dace was clarified by identifying ion transporters, channel, and their related molecules that become highly induced when dace are transferred from neutral to acidic water. Furthermore, the molecules responsible for the acid tolerance were mainly expressed in chloride cells. (3) Osmoregulation in teleost fish is achieved largely through active salt transport by specialized cells known as chloride cells. Reflecting their extraordinary power of ion transport, chloride cells are rich in Na, K-ATPase. Exploiting this unique property of the chloride cell, we succeeded in identifying a K channel likely to be functionally coupled with Na, K-ATPase ; identification of such a K channel has been a long-standing goal in animal physiology. (4) Autoradiographic localization of eel NP receptor revealed an unexpectedly dense localization in the gill chondrocytes, suggesting tight relationship between the NP system and bone metabolism, which then open a new avenue in the field of bone research.