|SANGHA, VISHAL - University Of Toronto|
|LANGE, ANGELA - University Of Toronto|
|ORCHARD, IAN - University Of Toronto|
Submitted to: Journal of Insect Biochemistry and Molecular Biology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/21/2019
Publication Date: N/A
Interpretive Summary: Insect pests have developed resistance to several conventional pesticides, and new approaches are needed for pest management. Although neuropeptides (short chains of amino acids) serve as potent messengers in insects to regulate vital functions, the neuropeptides hold little promise as pest control agents because they can be degraded in the target pest. New, selective control agents may be developed by designing mimics of these neuropeptides that resist degradation and either inhibit or over-stimulate critical neuropeptide-regulated life functions. The mimics can also elucidate complex hormonal mechanisms that aid in development of novel pest control methods. Neuropeptides of the ‘kinin’ and ‘CAPA’ classes regulate aspects of feeding, digestion and water balance that are critical for insect survival. Research was conducted that demonstrates that stable mimics of the kinins and CAPAs interfere with blood feeding of the assassin bug, an insect that transmits Chaga’s disease to humans. A kinin mimic caused a significant reduction in the blood meal, whereas a CAPA mimic that blocks CAPA activity conversely increased the blood meal size. The mimics of the two hormone classes also aided in the elucidation of a novel interaction between the two hormones in the digestive system during post-feeding excretion, an event that leads to disease transmission. The interaction highlights the coordination required by the hormonal system in carrying out critical life functions. The synthetic mimics therefore disrupt feeding, digestion and disease transmission in this important medical pest. This work provides templates for the design of neuropeptide-like compounds capable of disrupting the critical life function of feeding, digestion and excretion in these insect pests and brings us one step closer to the development of practical neuropeptide-like substances that will be effective in controlling insect pests that transmit deadly diseases in an environmentally friendly fashion.
Technical Abstract: In the Chagas disease vector Rhodnius prolixus, the kinin and CAPA family of neuropeptides are implicated in feeding and diuresis-related behaviours, with Rhopr-kinins stimulating contractions of the midgut and hindgut, and RhoprCAPA-2 functioning as an anti-diuretic hormone. The use of neuropeptide mimetics is a promising approach to vector control as they can disrupt behaviours associated with disease transmission. The current study examined the effects of kinin and CAPA neuropeptides and their analogs on feeding and diuresis, and on hindgut contractions and Malpighian tubule (MT) secretion in R. prolixus. The biostable Aib-containing kinin analog 2139[Phi1]wp-2 was found to have antifeedant effects, while the CAPA analog 2129-SP3[Phi3]wp-2 induced the intake of a larger blood meal, and increased the rate of post-prandial rapid diuresis. RhoprCAPA-2 potentiated the hindgut contractions induced by Rhopr-kinin 2, with no effects observed only with any of the CAPA neuropeptides. A potentiation was also observed with the CAPA analog on 5-HT-stimulated increases in frequency of hindgut contractions, while RhoprCAPA-2 inhibited this 5-HT mediated stimulation. The CAPA analog induced hindgut contractions and prevented the inhibition induced by RhoprCAPA-2 on 5-HT-stimulated MT secretion. These results demonstrate novel interactions between Rhopr-kinin and RhoprCAPA-2 on the hindgut, possibly influencing post-feeding excretion. The effects of the neuropeptide analogs highlight their value as lead compounds, given their ability to interfere with epidemiologically-relevant behaviours.