Physiological effects of biostable kinin and CAPA analogs in the Chagas disease vector, Rhodnius prolixus

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, salivary glands, and hindgut, and RhoprCAPA-2 functioning as an anti-diuretic hormone. The current study examined the effects of kinin and CAPA neuropeptides and their analogs on feeding and diuresis, and on hindgut contractions and MT fluid secretion in R. prolixus. The biostable Aib-containing kinin analog 2139[Φ1]wp-2 was found to have antifeedant effects, and to be more potent than Rhopr-kinin 2 in stimulating hindgut contractions. The CAPA analog 2129-SP3[Φ3]wp-2 induced the intake of a larger blood meal, and increased the rate of post-prandial rapid diuresis. RhoprCAPA-2, but not its analog, potentiated hindgut contractions induced by Rhopr-kinin 2. Potentiation was observed with the CAPA analog on 5-HT-stimulated increases in frequency of hindgut contractions, whereas 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 kinin analog is a potent agonist of the kinin receptor, and the CAPA analog an antagonist of the CAPA receptor. The use of neuropeptide mimetics is a promising approach to vector control as they can disrupt behaviours, and the effects of these neuropeptide analogs highlight their value as lead compounds, given their ability to interfere with epidemiologically-relevant behaviours.