Bioavailability of insect neuropeptides: The PK/PBAN family as a case study

The ability of unmodified linear peptides to penetrate the insect cuticle and exert bioactivity (e.g., stimulation of sex pheromone biosynthesis) was tested by topical application onto Heliothis peltigera moths of four insect neuropeptides (Nps) of the pyrokinin (PK)/pheromone biosynthesis activating neuropeptide (PBAN) family: Helicoverpa zea PBAN (Hez-PBAN), Pseudaletia (Mythimna) separata pheromonotropin (PT), Leucophaea maderae PK (LPK) and Locusta migratoria myotropin (Lom-MT-II). The time kinetic of the peptides applied in double distilled water (DDW) or dimethylsulfoxide (DMSO) was tested and the activities of topically applied and injected peptides were compared. The results clearly indicated that all four peptides were highly potent but with differing activities in the two solvents: PBAN was most active in water, and PT in DMSO. The activity of PBAN in DDW lasted up to 8 h post-application and its activity in this solvent showed a faster onset and a longer persistence than in DMSO. LPK and MT differed less in their kinetics between the two solvents. Topically applied PBAN at 1 nmol exhibited an equivalent or even significantly higher potency than the injected peptide at several different times post-treatment. Similar results were obtained with topically applied and injected LPK. The present results add important information on the bioavailability of unmodified linear peptides in moths, clearly indicate that linear hydrophilic peptides can penetrate the cuticle by contact application in aqueous solutions and in organic solvents very efficiently, reach their target organ and activate it.