title: Functional analysis of synthetic insectatachykinin analogs on recombinant neurokinin receptor expressing cell lines.
abstract: 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.
authors.affiliation: Laboratory for Developmental Physiology and Molecular Biology, Zoological Institute K.U. Leuven, Naamsestraat 59, Belgium.
authors.forename: Herbert
authors.initials: H
authors.lastname: Torfs
authors.forename: Karl E
authors.initials: KE
authors.lastname: Akerman
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Nachman
authors.forename: Hendrica B
authors.initials: HB
authors.lastname: Oonk
authors.forename: Michel
authors.initials: M
authors.lastname: Detheux
authors.forename: Jeroen
authors.initials: J
authors.lastname: Poels
authors.forename: Tom Van
authors.initials: TV
authors.lastname: Loy
authors.forename: Arnold De
authors.initials: AD
authors.lastname: Loof
authors.forename: Rob H
authors.initials: RH
authors.lastname: Meloen
authors.forename: Gilbert
authors.initials: G
authors.lastname: Vassart
authors.forename: Marc
authors.initials: M
authors.lastname: Parmentier
authors.forename: Jozef Vanden
authors.initials: JV
authors.lastname: Broeck
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D016466:CHO Cells; D002460:Cell Line; D006224:Cricetinae; D018039:Receptors, Tachykinin / Q000187:drug effects*; D011994:Recombinant Proteins / Q000187:drug effects; D015320:Tachykinins / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D018039:Receptors, Tachykinin; D011994:Recombinant Proteins; D015320:Tachykinins