Author:

Abstract:

Aequorin-based assays for stable fly, Stomoxys calcitrans, (STKR) and human (NK1, NK2) neurokinin-like receptors were utilised to study the effects of C-terminal amino acid changes in synthetic tachykinin-like peptides. C-terminally (Arg to Met) substituted analogs of the insectatachykinin-related peptide, Lom-TK I, showed increased agonistic potencies in luminescent assays for human NK1- and NK2-receptors, whereas they showed reduced potencies in the STKR-assay. The opposite effects were observed when C-terminally (Met to Arg) substituted analogs of substance P were analysed. These substance P analogs proved to be very potent STKR-agonists. On the other hand, Lom TK-LMa, was shown to be a very potent NK1-agonist and was suggested to have more substance-P-mimetic than neurokinin-A-mimetic properties. NK1- and NK2-receptor agonists appeared to be more sensitive to changes at the penultimate amino acid position than STKR-agonists. This is also reflected in the sequence conservation that is observed in the naturally occurring tachykinin subgroups ('FXGLMa' versus 'FX1GX2Ra'). This differential Arg/Met preference appears to be a major co-evolutionary change between insect and human peptide-receptor couples.