Sulfakinin Neuropeptides and Their Receptors in Insects: Molecular Signalling, Physiological Diversity, and Pest...

Sulfakinin (SK) peptides are the insect members of the ancient cholecystokinin (CCK)/gastrin superfamily, defined by a sulfated tyrosine near the C-terminus and a C-terminally amidated heptapeptide core, modifications essential for receptor activity. Although SK peptides share C-terminal similarity with vertebrate CCK-8 and gastrin, this homology is pharmacologically incomplete: both Drosophila sulfakinin receptors cluster in an arthropod-specific clade absent from vertebrate receptor families, and cross-species bioassays confirm receptor-level incompatibility. This review synthesizes current knowledge of SK structure, receptor biology, signal transduction, and physiological function across insect orders to evaluate the SK-receptor axis with emphasis on factors that may inform future pest-management applications. SKR complement ranges from one gene in Hymenoptera and Lepidoptera to two paralogous receptors in several Diptera and Coleoptera, arising from independent lineage-specific duplications. Both Ca²⁺ and cAMP second messenger arms are engaged in species-dependent combinations governed by G-protein coupling selectivity. SK peptides regulate meal termination, fat body lipid and glycogen metabolism, ecdysteroid-mediated moulting, reproductive behaviour, and agonistic signalling, with these functions partitioned among specific receptor subtypes, neural circuits, and peripheral tissues. In laboratory studies of economically significant pest species, RNAi-mediated SK-receptor silencing disrupts feeding, development, and fecundity, whereas biostable peptidomimetics represent a promising but still exploratory chemical approach. Receptor coupling identity in phytophagous crop pests, validated field-compatible dsRNA delivery, and ecological safety remain major unresolved barriers to practical application.