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Copeptin: More than Just a Surrogate Biomarker
Author(s) -
Haddock Christopher J.,
Wille Hannah M.,
Yosten Gina L.C.,
Samson Willis K.
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.714.4
Subject(s) - copeptin , g protein coupled receptor , receptor , biomarker , biology , computational biology , biochemistry , vasopressin , endocrinology
Copeptin is a 39 amino acid peptide derived from the vasopressin preprohormone. The function of vasopression is well characterized; however, the receptor and physiological function of copeptin remain unknown. These peptides are secreted at a 1:1 ratio, indicating that the actions of vasopression could “mask” the effects of copeptin. Thus, the physiologic effects of copeptin have been difficult to ascertain. Currently, copeptin is used as a surrogate biomarker for vasopression secretion due to the short half‐life of and difficulty measuring vasopression, but the biological activity of copeptin has not been confirmed. To evaluate the potential biological effects of copeptin, we exposed three cell types (HEK293, KATOIII, and ARPE19) to increasing concentrations of copeptin. Using real time quantitative PCR we have discovered that incubation with 100nM copeptin leads to increases in mRNA expression of the early transcriptional activation marker c‐FOS in all three cell types. Transcriptional activation indicates that copeptin is working through a receptor, and because the effects of vasopressin are mediated through G protein‐coupled receptors (GPCRs) V1, V2, and V3, we hypothesize that copeptin also signals through a GPCR. We are testing this hypothesis using a “deductive ligand‐receptor matching strategy” developed in our lab. Candidates for a potential receptor fall into a class of GPCRs with no known ligand, Orphan GPCRs. To narrow the pool of candidate receptors for copeptin, we have compared expression profiles of all orphan GPCRs in the copeptin‐responsive cell lines. This strategy generated a short list of orphan GPCRs expressed by all three cell types. One of the candidate receptors expressed in all responding cell types is likely responsible for mediating the transcriptional effects of copeptin. We are using knockdown/rescue experiments to determine which receptor copeptin is signaling through. We also are developing an animal model to determine the physiologic effects of copeptin, leading to a better understanding of the function of this peptide. Support or Funding Information NIH HL121456