title: Proinsulin C-peptide and its analogues induce intracellular Ca2+ increases in human renal tubular cells.
abstract: Based on the findings that proinsulin C-peptide binds specifically to cell membranes, we investigated the effects of C-peptide and related molecules on the intracellular Ca2+ concentration ([Ca2+]i) in human renal tubular cells using the indicator fura-2/AM. The results show that human C-peptide and its C-terminal pentapeptide (positions 27-31, EGSLQ), but not the des (27-31) C-peptide or randomly scrambled C-peptide, elicit a transient increase in [Ca2+]i. Rat C-peptide and rat C-terminal pentapeptide also induce a [Ca2+]i response in human tubular cells, while a human pentapeptide analogue with Ala at position 1 gives no [Ca2+]i response, and those with Ala at positions 2-5 induce responses with different amplitudes. These results define a species cross-reactivity for C-peptide and demonstrate the importance of Glu at position 1 of the pentapeptide. Preincubation of cells with pertussis toxin abolishes the effect on [Ca2+]i by both C-peptide and the pentapeptide. These results are compatible with previous data on C-peptide binding to cells and activation of Na-,K+ATPase. Combined, all data show that C-peptide is a bioactive peptide and suggest that it elicits changes in [Ca2+]i via G-protein-coupled pathways, giving downstream enzyme effects.
authors.affiliation: Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
authors.forename: J
authors.initials: J
authors.lastname: Shafqat
authors.forename: L
authors.initials: L
authors.lastname: Juntti-Berggren
authors.forename: Z
authors.initials: Z
authors.lastname: Zhong
authors.forename: K
authors.initials: K
authors.lastname: Ekberg
authors.forename: M
authors.initials: M
authors.lastname: Köhler
authors.forename: P O
authors.initials: PO
authors.lastname: Berggren
authors.forename: J
authors.initials: J
authors.lastname: Johansson
authors.forename: J
authors.initials: J
authors.lastname: Wahren
authors.forename: H
authors.initials: H
authors.lastname: Jörnvall
mesh_terms: D000818:Animals; D002096:C-Peptide / Q000031:analogs & derivatives* / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D003593:Cytoplasm / Q000378:metabolism; D006801:Humans; D007684:Kidney Tubules / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D051381:Rats; D013045:Species Specificity
chemical_list: D002096:C-Peptide; D002118:Calcium