Chemical studies of pheromone receptors in insects

In the current molecular model for insect olfaction, pheromones are recognized in a minimum‐energy conformation by specific receptor proteins in a dendritic membrane following their binding‐protein‐mediated transit through the extracellula sensory lymph. Binding to the receptor protein then triggers a G‐protein‐linked phospholipase C, which releases a short pulse of the second messenger inositol 1,4,5‐trisphate (IP3). IP3 may act via its receptor to mobilize Ca+ + ions, eventually leading to a transmembrane ion current; alternatively, IP3 may directly gate the ion channel. To understand this process, we have synthesized photoaffinity labels for the pheromone receptor sites and for the IP3 receptor sites. The latter probe, [125I]‐ASA‐IP3, is now being employed in joint projects to identify membrane IP3 receptors in the rat brain, locust brain, rat olfactory cilia, catfish olfactory cilia, and in cockroach and moth sensilla. Fluorine‐substituted pheromone analogs have also been synthesized as probes of receptor site hydrophobicity. The rationale for this approach is presented, and biological studies with selectively‐fluorinated analogs of (Z)‐5‐decenyl acetate (Z5‐10:Ac), (Z)‐7‐dodecenyl acetate (Z7‐12:Ac), (Z)‐9‐dodecenyl acetate (Z9‐12:Ac), (Z)‐9‐tetradecenyl acetate (Z9‐14:Ac), (Z)‐11‐hexadecenal (Z11‐16:Al), and several functional group derivatives for a number of economically important moth species are described.