RECEPTOR-BINDING PROFILES OF NPY ANALOGS AND FRAGMENTS IN DIFFERENT TISSUES AND CELL-LINES

To investigate receptor selectivity and possible species selectivity o f a number of NPY analogues and fragments, receptor binding studies we re performed using cell lines and membranes of several species. NPY di splays 4-25-fold higher affinity for the Y-2 receptor than for the Y-1 receptor. The affinity of [Leu(31), Pro(34)]NPY is 7-60-fold higher f or the Y-1 receptor when compared with the Y-2 subtype. Species select ivity within the Y-2 receptors is demonstrated by PYY(3-36), NPY(2-36) , NPY(27-36), and NPY(26-36). It is shown that NPY(22-36) is species s elective for the human Y-2 subtype (K-i of 0.3 nM) compared with the r abbit and rat Y-2 receptor (K-i of 2 and 10 nM, respectively). PYY(3-3 6) displays highest affinity for the human and rabbit Y-2 subtype (K-i of 0.03 and 0.17 nM). The screening of NPY analogues and fragments re vealed that highest affinity for the human Y-2 receptor is shown by NP Y(2-36) and PYY(3-36). In addition, PYY(3-36) and NPY(2-36) are not on ly subtype selective, but also species selective.