A novel function of calcitonin gene-related peptide in body fluid Cl- homeostasis.
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.
Institute of Fishery Science, National Taiwan University, Taipei, Taiwan Institute of Cellular and Organismic Biology, Academia Sinica, Taipei, Taiwan.
Yi-Fang
YF
Wang
Muséum National d'Histoire Naturelle, Sorbonne Universités, Research Unit BOREA, Biology of Aquatic Organisms and Ecosystems, CNRS 7208, IRD207, UPMC, UCBN, Paris, France.
Anne-Gaëlle
AG
Lafont
Institute of Cellular and Organismic Biology, Academia Sinica, Taipei, Taiwan.
Yi-Chun
YC
Lee
Institute of Fishery Science, National Taiwan University, Taipei, Taiwan Institute of Cellular and Organismic Biology, Academia Sinica, Taipei, Taiwan pphwang@gate.sinica.edu.tw.
Pung-Pung
0000-0002-5534-2812
PP
Hwang
D000818:Animals; D001826:Body Fluids / Q000737:chemistry*; D015740:Calcitonin Gene-Related Peptide / Q000502:physiology*; D002712:Chlorides / Q000737:chemistry*; D006706:Homeostasis; D012333:RNA, Messenger; D015027:Zebrafish / Q000502:physiology; D029961:Zebrafish Proteins / Q000502:physiology*
D002712:Chlorides; D012333:RNA, Messenger; D029961:Zebrafish Proteins; D015740:Calcitonin Gene-Related Peptide
Cl− homeostasis; cgrp; ionocyte; ncc2b; zebrafish