ARS | Publication request: PHARMACOLOGY OF STOMOXYTACHYKININ RECEPTOR DEPENDS ON SECOND MESSENGER SYSTEM

Submitted to: Peptides
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: July 12, 2004
Publication Date: January 1, 2005
Citation: Poels, J., Nachman, R.J., Akerman, K.E., Oonk, H.B., Guerrero, F., De Loof, A., Janecka, A.E., Torfs, H., Vanden Broeck, J. 2005. Pharmacology of stomoxytachykinin receptor depends on second messenger system. Peptides. 26:109-114.

Interpretive Summary: Because of problems with the development of resistance to conventional pesticides, there is a critical need for new concepts and alternative approaches in controlling insect pests. The basic premise of this research is that neuropeptides (short chains of amino acids) serve as potent messengers in insects to regulate vital functions. Nevertheless, these neuropeptides in and of themselves hold little promise as pest control agents because of susceptibility to being degraded in the target pest, and inability to pass through the outside skin (cuticle) and/or digestive tract. We must design neuropeptide mimics that resist degradation by enzymes in the digestive tract and blood of pest insects and interact with the active site within the agricultural pest in such a way as to either over-activate or block critical, neuropeptide-regulated life functions. We report on the specific mechanism by which the active site of the 'insectatachykinin' neuropeptide class within the stable fly can initiate two different regulatory outcomes, and how this is dependant on the structure of the neuropeptide messenger. This discovery will aid in the design of neuropeptide-like compounds capable of disrupting water balance and digestion in these livestock pests. The work brings us one step closer to the development of practical neuropeptide-like substances that will be effective in controlling pest insects in an environmentally friendly fashion.

Technical Abstract: STKR is a neurokinin receptor derived from the stable fly, Stomoxys calcitrans. Insect tachykinin-related peptides, also referred to as 'insectatachykinins', produce dose-dependent calcium and cyclic AMP responses in cultured Drosophila melanogaster Schneider 2 (S2) cells that were stably transfected with the cloned STKR cDNA. Pronounced differences in pharmacology were observed between agonist-induced calcium and cyclic AMP responses. The results indicate that the pharmacological properties of STKR depend on its coupling to a unique second messenger system. Therefore, a model postulating the existence of multiple active receptor conformations is proposed. This article presents the first evidence that an insect peptide receptor with dual coupling properties to second messenger systems can display agonist-dependent functional differences.