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

STKR is a G protein-coupled receptor that was cloned from the stable fly, S tomoxys 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 pe ptides, also referred to as "insectatachykinins," produce dose-dependent ca lcium responses in Drosophila melanogaster Schneider 2 cells, which are sta bly transfected with this receptor (S2-STKR). These responses do not depend on the presence of extracellular Ca2+-ions. A rapid agonist-induced increa se of inositol 1,4,5-trisphosphate (IP3) is observed. This indicates that t he agonist-induced cytosolic Ca2+-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-re ceptors on STKR-expressing insect cells. The results show that spantide II, a potent substance P antagonist, is a real antagonist of insectatachykinin s on STKR. We have also tested the activity of a variety of natural insecta tachykinin analogs by microscopic image analysis of calcium responses in S2 -STKR cells. At a concentration of 1 muM, almost all natural analogs produc e a significant calcium rise in stable S2-STKR cells. Interestingly, Ste-TK , an insectatachykinin that was recently discovered in the stable fly (S. c alcitrans), also proved to be an STKR-agonist. Stc-TK, a potential physiolo gical ligand for STKR, contains an Ala-residue (or A) instead of a highly c onserved Gly-residue (or G). Arch. Insect Biochem. Physiol. 48:39-49, 2001. (C) 2001 Wiley-Liss, Inc.