Myotropic Activities of Tick Pyrokinin Neuropeptides and Analog in Feeding Tissues of Hard Ticks (Ixodidae)

Xiong, Caixing; Wulff, Juan Pedro; Nachman, Ronald J.; Pietrantonio, Patricia V.

doi:10.3389/fphys.2021.826399

Cited by 8 publications

(18 citation statements)

References 51 publications

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“…However, a lower expression was observed in hindgut, and a very low expression was observed in other tissues, such as midgut, Malpighian tubules and salivary glands [ 23 , 24 ]. This expression pattern suggests a functional role in feeding and reproduction, possibly associated with the regulation of myotropic activity, as we recently reported [ 25 ].…”

Section: Introductionsupporting

confidence: 80%

“…Based on the results of this study, our recent work [ 25 ] and previous evidence in insect tissues reviewed in [ 9 ], the PK tick signaling system appears to activate muscles involved in feeding. Unlike blood-feeding insects that feed through blood vessels, ticks are pool feeders, with a complex and active feeding mechanism [ 61 ].…”

Section: Discussionsupporting

confidence: 64%

“…4 ), but further studies are needed to determine if this or both phases were compromised. The hypothesis is further supported by our recent study that demonstrated the myotropic activity of PK in feeding-related tissues of two tick species, R. sanguineus and I. scapularis [ 25 ], being the first report to explore the functional activity of PK and a PK analog in ticks. Additional evidence supports that the pyrokinin signaling system is associated with the feeding-related tissues in arthropods.…”

Section: Discussionmentioning

confidence: 54%

“…Pyrokinins are pleiotropic neuropeptides in insects, and one of their functions is to promote muscle contractions [ 8 ]. While we recently reported that pyrokinins and a pyrokinin peptide analog elicit the contraction of feeding-related tissues of R. sanguineus in vitro [ 25 ], the pleiotropic functions of the pyrokinin signaling system in ticks are still unexplored. Therefore, we performed loss-of-function experiments by RNAi of the pyrokinin receptor in live females of R. microplus to further investigate the physiological significance of the pyrokinin signaling system in ticks and to assess if this GPCR could be a good candidate for control interventions (e.g.…”

Section: Discussionmentioning

confidence: 99%

“…PK/PBAN/DH orthologous sequences from insects, and their receptors, have been identified in ticks [ 4 , 10 , 21 – 23 ]. To date, only two functional studies with tick PK recombinant receptors of R. microplus [ 23 ] and I. scapularis [ 24 ] have been conducted, and only recently we reported the first in vitro analysis of tick pyrokinin 2 myotropic activity on I. scapularis and Rhipicephalus sanguineus tissues [ 25 ].…”

Section: Introductionmentioning

confidence: 99%

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Pyrokinin receptor silencing in females of the southern cattle tick Rhipicephalus (Boophilus) microplus is associated with a reproductive fitness cost

et al. 2022

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Background Rhipicephalusmicroplus is the vector of deadly cattle pathogens, especially Babesia spp., for which a recombinant vaccine is not available. Therefore, disease control depends on tick vector control. However, R.microplus populations worldwide have developed resistance to available acaricides, prompting the search for novel acaricide targets. G protein-coupled receptors (GPCRs) are involved in the regulation of many physiological processes and have been suggested as druggable targets for the control of arthropod vectors. Arthropod-specific signaling systems of small neuropeptides are being investigated for this purpose. The pyrokinin receptor (PKR) is a GPCR previously characterized in ticks. Myotropic activity of pyrokinins in feeding-related tissues of Rhipicephalussanguineus and Ixodesscapularis was recently reported. Methods The R.microplus pyrokinin receptor (Rhimi-PKR) was silenced through RNA interference (RNAi) in female ticks. To optimize RNAi, a dual-luciferase assay was applied to determine the silencing efficiency of two Rhimi-PKR double-stranded RNAs (dsRNA) prior to injecting dsRNA in ticks to be placed on cattle. Phenotypic variables of female ticks obtained at the endpoint of the RNAi experiment were compared to those of control female ticks (non-injected and beta-lactamase dsRNA-injected). Rhimi-PKR silencing was verified by quantitative reverse-transcriptase PCR in whole females and dissected tissues. Results The Rhimi-PKR transcript was expressed in all developmental stages. Rhimi-PKR silencing was confirmed in whole ticks 4 days after injection, and in the tick carcass, ovary and synganglion 6 days after injection. Rhimi-PKR silencing was associated with an increased mortality and decreased weight of both surviving females and egg masses (P < 0.05). Delays in repletion, pre-oviposition and incubation periods were observed (P < 0.05). Conclusions Rhimi-PKR silencing negatively affected female reproductive fitness. The PKR appears to be directly or indirectly associated with the regulation of female feeding and/or reproductive output in R.microplus. Antagonists of the pyrokinin signaling system could be explored for tick control. Graphical abstract

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Section: Introductionsupporting

confidence: 80%

Section: Discussionsupporting

confidence: 64%

Section: Discussionmentioning

confidence: 54%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Pyrokinin receptor silencing in females of the southern cattle tick Rhipicephalus (Boophilus) microplus is associated with a reproductive fitness cost

et al. 2022

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Functional expression and characterization of CAPA receptor in the digestive tract and life stages of Drosophila suzukii, and differential activities with insect PRXamide peptides

Price,

Jang,

Parks

et al. 2024

Arch Insect Biochem Physiol

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Spotted‐wing drosophila, Drosophila suzukii (Matsumura), is an invasive vinegar fly that is a major threat to the small fruits industries globally. Insect capa genes encode multiple neuropeptides, including CAPA‐periviscerokinin (CAPA‐PVK) peptides, that are specifically known to cause diuresis or anti‐diuresis in various organisms. Here we identified and characterized a corresponding G protein‐coupled receptor (GPCR) of the D. suzukii CAPA‐PVK peptides: CAPA receptor (CAPA‐R). To better characterize the behavior of D. suzukii CAPA‐R, we used insect cell‐based functional expression assays to evaluate responses of CAPA‐R against D. suzukii CAPA‐PVKs, CAPA‐PVKs from five species in Insecta, one species from Mollusca, modified CAPA‐PVK peptides, and some PRXamide family peptides: pyrokinin (PK), diapause hormone (DH), and ecdysis‐triggering hormone (ETH). Functional studies revealed that the D. suzukii CAPA‐R is strongly activated by both of its own natural D. suzukii CAPA‐PVKs, and interestingly, it was strongly activated by other CAPA‐PVK peptides from Frankliniella occidentallis (Thysanoptera), Solenopsis invicta (Hymenoptera), Helicoverpa zea (Lepidoptera) and Plutella xylostella (Lepidoptera). However, D. suzukii CAPA‐R was not activated by Mollusca CAPA‐PVK or the other PRXamide peptides. Gene expression analyses showed that the CAPA‐R was highly expressed in the Malpighian tubules and moderately in hindgut compared to other digestive organs or the rest of body, supporting diuretic/antidiuretic functionality. When compared across life stages of D. suzukii, expression of CAPA‐R was approximately 1.5x greater in the third instar than the other stages and minimally detected in the eggs, 4‐day old pupae and 3‐day old adults. Our results functionally characterized the D. suzukii CAPA‐R and a few short peptides were identified as potential biological targets to exploit the CAPA‐R for D. suzukii management.

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Target‐based discovery of antagonists of the tick (Rhipicephalus microplus) kinin receptor identifies small molecules that inhibit midgut contractions

Henriques‐Santos,

Baker,

Zhou

et al. 2024

Pest Management Science

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BACKGROUNDA GPCR (G protein‐coupled receptor) target‐based approach was applied to identify antagonists of the arthropod‐specific tick kinin receptor. These small molecules were expected to reproduce the detrimental phenotypic effects that had been observed in Rhipicephalus microplus females when the kinin receptor was silenced by RNA interference. Rhipicephalus microplus, the southern cattle tick, cattle fever tick, or Asian blue tick, is the vector of pathogenic microorganisms causing the deadly bovine babesiosis and anaplasmosis. The widespread resistance to acaricides in tick populations worldwide emphasizes that exploring novel targets for effective tick control is imperative.RESULTSFifty‐three structural analogs of previously identified tick kinin antagonists were screened in a ‘dual‐addition’ calcium fluorescence assay using a CHO‐K1 cell line expressing the tick kinin receptor. Seven molecules were validated as non‐cytotoxic antagonists, four of which were partial (SACC‐0428764, SACC‐0428780, SACC‐0428800, and SACC‐0428803), and three were full antagonists (SACC‐0428799, SACC‐0428801, and SACC‐0428815). Four of these antagonists (SACC‐0428764, SACC‐0428780, SACC‐0428799, and SACC‐0428815) also inhibited the tick midgut contractions induced by the myotropic kinin agonist analog 1728, verifying their antagonistic bioactivity. The small molecules were tested on recombinant human neurokinin (NK) receptors, the one most similar to the invertebrate kinin receptors. Most molecules were inhibitors of the NK1 receptor, except SACC‐0412066, a previously identified tick kinin receptor antagonist, which inhibited the NK1 receptor only at the highest concentration tested (25 μm). None of the molecules inhibited the NK3 human receptor.CONCLUSIONMolecules identified through this approach could be useful probes for studying the tick kinin signaling system and midgut physiology. © 2024 The Author(s). Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

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Myotropic Activities of Tick Pyrokinin Neuropeptides and Analog in Feeding Tissues of Hard Ticks (Ixodidae)

Cited by 8 publications

References 51 publications

Pyrokinin receptor silencing in females of the southern cattle tick Rhipicephalus (Boophilus) microplus is associated with a reproductive fitness cost

Pyrokinin receptor silencing in females of the southern cattle tick Rhipicephalus (Boophilus) microplus is associated with a reproductive fitness cost

Functional expression and characterization of CAPA receptor in the digestive tract and life stages of Drosophila suzukii, and differential activities with insect PRXamide peptides

Target‐based discovery of antagonists of the tick (Rhipicephalus microplus) kinin receptor identifies small molecules that inhibit midgut contractions

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