Pharmacological characterization of the piscf - allatostatin receptor in carausius morosus

Abstract

Allatostatins (ASTs) are multifunctional insect neuropeptides that suppress juve-nile hormone (JH) synthesis and feeding behavior. Three different classes of ASTs in in-sects are known as FGLa/ASTs (A-type), MIP/ASTs (B-type) and PISCF/ASTs (C-type). Each type of ASTs exert its activity through binding to its cognate G protein coupled receptor families, called as Allatostatin receptors (AstRs). Very little is known on how JH synthesis is regulated and how AST/AstR system regulates this process. AstRs are also potential targets for pesticide development, since their activation negatively modulates insect growth and feeding-related processes. A transcript from an invasive African pest, Carausius morosus, which shows high sequence similarity to other insect PISCF/AST receptors was previously identified by our group. In this study, we characterized the phar-macological properties and early signaling events of this PISCF/AST receptor (CamAstR-C) by means of FRET using a heterologous expression system. A dose-dependent activa-tion of Gαi1 and Gαo were detected upon stimulation of CamAstR-C. Receptor coupling with Gβγ subunits was observed only in the presence of Gαi1 or Gαo, but not other Gα subunits. A partial inhibition of adenylyl cyclase 5-mediated cAMP production upon re-ceptor activation with PISCF/AST and a dose-dependent interaction between β-arrestin2 and the receptor was detected. In summary, a PISCF/AST receptor from Carausius mo-rosus has been functionally characterized, activated by Drosophila PISCF/AST, but not Drosophila FGLa/ASTs.