| Popis: |
Relaxin, a two-chain, three disulfide-bonded member of the insulin superfamily, is produced principally by the corpus luteum of the ovary during pregnancy. It has long been considered that its primary role is that of preparing the birth tract for the delivery of the young [1]. However, the recent demonstration of binding sites for relaxin in the heart and brain of both male and female rats points to a wider physiological role [2, 3]. Studies with synthetic relaxin have shown the peptide possesses powerful chronotropic and inotropic activity [4] and to directly increase neuronal activity in regions of the lamina terminalis and hypothalamus associated with fluid and electrolyte balance [5]. Like insulin, relaxin is made on the ribosome as a preprohormone which undergoes subsequent proteolytic processing to yield the native two-chain peptide. Curiously, the connecting C-peptide is approximately 103 residues in length, compared to the corresponding 25 residue peptide in proinsulin [6]. Studies with insulin have shown that C-peptide mimics as short as one residue are sufficient to effect efficient chain folding and correct disulfide bond pairing [7]. Furthermore, recombinant DNA-derived human Gene 2 relaxin may be readily and efficiently produced using an “ini” C-peptide of 13 residues. This C-peptide is then excised by treatment with specific endopeptidases [8]. Thus, the large length of the native relaxin C-peptide suggests that it may perhaps have an additional function or serve as a precursor to biologically active peptides. Support for this concept has recently arisen following the surprising finding that, in pharmacological doses, human proinsulin C-peptide has an insulin-like action [9, 10]. We therefore undertook the chemical synthesis of two fragments of rat relaxin Cpeptide and assayed these for both relaxin-like or relaxin-potentiating activity. |
