Functional analysis of synthetic insectatachykinin analogs on recombinant neurokinin receptor expressing cell lines.
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.
Torfs
Herbert
H
Laboratory for Developmental Physiology and Molecular Biology, Zoological Institute K.U. Leuven, Naamsestraat 59, Belgium.
Akerman
Karl E
KE
Nachman
Ronald J
RJ
Oonk
Hendrica B
HB
Detheux
Michel
M
Poels
Jeroen
J
Loy
Tom Van
TV
Loof
Arnold De
AD
Meloen
Rob H
RH
Vassart
Gilbert
G
Parmentier
Marc
M
Broeck
Jozef Vanden
JV
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*
D018039:Receptors, Tachykinin; D011994:Recombinant Proteins; D015320:Tachykinins