Substitution of conserved glycine residue by alanine in natural and synthetic neuropeptide ligands causes partial agonism at the stomoxytachykinin receptor

Journal of Neurochemistry
J PoelsJozef Vanden Broeck

Abstract

A few naturally occurring insect tachykinin-related peptides, such as stomoxytachykinin (Stc-TK), contain an Ala-residue instead of the highly conserved Gly-residue that is present in most other members of this peptide family. Stc-TK is a potent, partial agonist of the stable fly (Stomoxys calcitrans) tachykinin receptor, STKR. By means of synthetic analogues, the Gly/Ala exchange, representing the addition of a single methyl group in the active core region of these peptides, was shown to be fully responsible for the generation of this partial agonism, which was also accompanied by an increase in agonistic potency. Surprisingly, this Ala-dependent reduction in maximal response levels was only observed for the agonist-induced cellular calcium rise. Stomoxytachykinin, Stc-TK, did not display partial agonism for the STKR-mediated cyclic AMP response. A possible explanation for this differential partial agonism is that the Gly-containing and Ala-replaced peptides recognize and stabilize active receptor conformations that differ in their functional coupling efficacies towards these response pathways. Drosotachykinins, Drm-TK, tachykinin-like peptides encoded in the fruit fly genome, were shown to be STKR-agonists. Interestingly, one...Continue Reading

Citations

Sep 29, 2009·Peptides·Tom Van LoyJozef Vanden Broeck
Jan 1, 2005·Peptides·Jeroen PoelsJozef Vanden Broeck
Dec 3, 2014·Insect Biochemistry and Molecular Biology·Heleen VerlindenAlison Mercer
Feb 25, 2006·The Journal of Pharmacology and Experimental Therapeutics·Jakub FichnaAnna Janecka
Mar 1, 2020·Biochimica Et Biophysica Acta. Molecular Cell Research·Xiaobai HeNaiming Zhou

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