A Surprise End to 20 Year Search for Selective Agonists for Rat Vasopressin V_(1b) Receptor

摘要

The design of selective agonists for the human and rat vasopressin (VP) V_(1b) receptors has proved to be an elusive goal. We recently reported a breakthrough in the discovery of the first selective agonist for the human V_(1b) receptor namely: d[Cha~4]AVP (A, Table 1). However, because it retains appreciable antidiuretic activity in the rat it is thus not a selective V_(1b) agonist in the rat. We subsequently reported that d[X~4]AVP analogs (where X = Leu, Orn, Arg) (peptides B-D, Table 1) are highly selective for the human V_(1b) receptor . However, in a very recent study we report that they are not selective V_(1b) agonists in the rat. In this study, peptides A-D were further modified at position 8 to give the d[X~4,Y~8]VP analogs (where X = Cha, Leu, Orn, Arg; Y = Lys, Orn, Dab, Dap) (peptides 1-13, Table 1).