title: Bioavailability of backbone cyclic PK/PBAN neuropeptide antagonists--inhibition of sex pheromone biosynthesis elicited by the natural mechanism in Heliothis peltigera females.
abstract: The bioavailability (i.e. ability to penetrate the insect cuticle, to reach the target organ and to exert bioactivity) of two backbone cyclic (BBC) pyrokinin/pheromone biosynthesis-activating neuropeptide (PK/PBAN) antagonistic peptides was tested by applying them topically to Heliothis peltigera females and monitoring the resulting inhibition of sex pheromone production elicited by the natural (endogenous) mechanism during scotophase. Peptides were applied at various time points before the onset of scotophase, in aqueous or organic solvents, and pheromone content was examined at the 5th or 6th hour of scotophase. Both peptides penetrated the cuticle very efficiently and inhibited sex pheromone biosynthesis elicited by the natural mechanism for up to 8 or 9 h after application. The degree of inhibition differed between solvents: those applied in double-distilled water (DDW) were more active than those applied in dimethylsulfoxide (inhibition by 53-73% and 15-38%, respectively, for BBC-25, and 46-67% and 36-40%, respectively for BBC-28). Peptides applied in dimethylsulfoxide and hexane exhibited slightly more persistent inhibitory activity than those applied in DDW. The solvents themselves did not affect sex pheromone production. Multiple applications (at -2, 0, +2 and +4 h) resulted in almost complete (87%) inhibition of sex pheromone biosynthesis, compared with 52% inhibition following a single application. The present study is the first demonstration of the ability of topically applied PK/PBAN antagonists to inhibit sex pheromone biosynthesis elicited by the natural mechanism in female moths, and provides important information on the bioavailability of BBC peptides and the mechanism responsible for sex pheromone production in these insects.
authors.affiliation: Department of Entomology, The Volcani Center, Bet Dagan, Israel.
authors.forename: Aliza
authors.initials: A
authors.lastname: Hariton
authors.forename: Orna
authors.initials: O
authors.lastname: Ben-Aziz
authors.forename: Michael
authors.initials: M
authors.lastname: Davidovitch
authors.forename: Miriam
authors.initials: M
authors.lastname: Altstein
mesh_terms: D000287:Administration, Topical; D000818:Animals; D001682:Biological Availability; D005260:Female; D009036:Moths / Q000187:drug effects / Q000378:metabolism*; D009479:Neuropeptides / Q000493:pharmacokinetics* / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000493:pharmacokinetics* / Q000494:pharmacology; D012724:Sex Attractants / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000378:metabolism; D012997:Solvents / Q000737:chemistry; D014867:Water / Q000737:chemistry
chemical_list: D009479:Neuropeptides; D010456:Peptides, Cyclic; D012724:Sex Attractants; D012997:Solvents; C079709:pheromone biosynthesis activating neuropeptide, Helicoverpa zea; C079229:pyrokinin; D014867:Water