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Peptides ; 23(11): 1999-2005, 2002 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-12431738

RESUMO

The activity of a series of synthetic tachykinin-like peptide analogs was studied by means of microscopic calcium imaging on recombinant neurokinin receptor expressing cell lines. A C-terminal pentapeptide (FTGMRa) is sufficient for activation of the stomoxytachykinin receptor (STKR) expressed in Schneider 2 cells. Replacement of amino acid residues at the position of the conserved phenylalanine (F) or arginine (R) residues by alanine (A) results in inactive peptides (when tested at 1microM), whereas A-replacements at other positions do not abolish the biological activity of the resulting insectatachykinin-like analogs. Calcium imaging was also employed to compare the activity of C-terminally substituted tachykinin analogs on three different neurokinin receptors. The results indicate that the major pharmacological and evolutionary difference between tachykinin-related agonists for insect (STKR) and human (NK1 and NK2) receptors resides in the C-terminal amino acid residues (R versus M). A single C-terminal amino acid change can turn an STKR-agonist into an NK-agonist and vice versa.


Assuntos
Receptores de Taquicininas/efeitos dos fármacos , Taquicininas/farmacologia , Sequência de Aminoácidos , Animais , Células CHO , Linhagem Celular , Cricetinae , Proteínas Recombinantes/efeitos dos fármacos , Taquicininas/química
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