Pharmacological characterization of STKR, an insect G protein-coupled receptor for tachykinin-like peptides.

Autor: Torfs H; Laboratory for Developmental Physiology and Molecular Biology, Zoological Institute, K.U. Leuven, Leuven, Belgium., Oonk HB, Broeck JV, Poels J, Van Poyer W, De Loof A, Guerrero F, Meloen RH, Akerman K, Nachman RJ
Jazyk: angličtina
Zdroj: Archives of insect biochemistry and physiology [Arch Insect Biochem Physiol] 2001 Sep; Vol. 48 (1), pp. 39-49.
DOI: 10.1002/arch.1056
Abstrakt: STKR is a G protein-coupled receptor that was cloned from the stable fly, Stomoxys calcitrans. Multiple sequence comparisons show that the amino acid sequence of this insect receptor displays several features that are typical for tachykinin (or neurokinin, NK) receptors. Insect tachykinin-related peptides, also referred to as "insectatachykinins," produce dose-dependent calcium responses in Drosophila melanogaster Schneider 2 cells, which are stably transfected with this receptor (S2-STKR). These responses do not depend on the presence of extracellular Ca(2+)-ions. A rapid agonist-induced increase of inositol 1,4,5-trisphosphate (IP(3)) is observed. This indicates that the agonist-induced cytosolic Ca(2+)-rise is caused by a release of Ca(2+) ions from intracellular calcium stores. The pharmacology of STKR is analyzed by studying the effects of the most important antagonists for mammalian NK-receptors on STKR-expressing insect cells. The results show that spantide II, a potent substance P antagonist, is a real antagonist of insectatachykinins on STKR. We have also tested the activity of a variety of natural insectatachykinin analogs by microscopic image analysis of calcium responses in S2-STKR cells. At a concentration of 1 microM, almost all natural analogs produce a significant calcium rise in stable S2-STKR cells. Interestingly, Stc-TK, an insectatachykinin that was recently discovered in the stable fly (S. calcitrans), also proved to be an STKR-agonist. Stc-TK, a potential physiological ligand for STKR, contains an Ala-residue (or A) instead of a highly conserved Gly-residue (or G). Arch.
(Copyright 2001 Wiley-Liss, Inc.)
Databáze: MEDLINE
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