PUBLICATION

A novel function of calcitonin gene-related peptide in body fluid Cl- homeostasis

Authors
Wang, Y.F., Lafont, A.G., Lee, Y.C., Hwang, P.P.
ID
ZDB-PUB-160617-4
Date
2016
Source
Proceedings. Biological sciences   283(1832): (Journal)
Registered Authors
Hwang, Pung Pung
Keywords
Cl− homeostasis, cgrp, ionocyte, ncc2b, zebrafish
MeSH Terms
  • Animals
  • Body Fluids/chemistry*
  • Calcitonin Gene-Related Peptide/physiology*
  • Chlorides/chemistry*
  • Homeostasis*
  • RNA, Messenger
  • Zebrafish/physiology
  • Zebrafish Proteins/physiology*
PubMed
27306053 Full text @ Proc. Biol. Sci.
Abstract
Vertebrates need to maintain extracellular chloride (Cl(-)) concentrations to ensure the normal operation of physiological processes; the transition from aquatic to terrestrial environments necessitated the development of sophisticated mechanisms to ensure Cl(-) homeostasis in the face of fluctuating Cl(-) levels. Zebrafish calcitonin gene-related peptide (CGRP), unlike its splice variant calcitonin, does not respond to environmental Ca(2+) levels. This study aimed to test the hypothesis that CGRP is involved in the control of body fluid Cl(-) homeostasis. Acclimation to high-Cl(-) artificial water stimulated the mRNA expression of cgrp and the receptor (crlr1) when compared with low-Cl(-) CGRP knockdown induced upregulation of the Na(+)-Cl(-) co-transporter (ncc2b), while overexpression of CGRP resulted in the downregulation of ncc2b mRNA synthesis and a simultaneous decrease in Cl(-) uptake in embryos. Consistent with these findings, knockdown of either cgrp or crlr1 was found to increase the density of NCC2b-expressing cells in embryos. This is the first demonstration that CGRP acts as a hypochloremic hormone through suppressing NCC2b expression and the differentiation of NCC-expressing ionocytes. Elucidation of this novel function of CGRP in fish body fluid Cl(-) homeostasis promises to enhance our understanding of the related physiology in vertebrates.
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