Year: 2022
Type: article
Abstract: The nematode parasite intestine absorbs nutrients, is involved in innate immunity, can metabolize xenobiotics and as we show here, is also a site of action of the anthelmintic, diethylcarbamazine. Diethylcarbamazine (DEC) is used to treat lymphatic filariasis and activates TRP-2, GON-2 & CED-11 TRP channels in Brugia malayi muscle cells producing spastic paralysis. DEC also has effects on ascarid nematode parasites. Using PCR techniques, we detected, in A. suum intestine, message for: Asu-trp-2, Asu-gon-2, Asu-ced-11, Asu-ocr-1, Asu-osm-9 and Asu-trpa-1. Comparison of amino-acid sequences of the TRP channels of B. malayi, and A. suum revealed noteworthy similarity, suggesting that the intestine of Ascaris will also be sensitive to DEC. We used Fluo-3AM as a Ca2+ indicator and observed characteristic unsteady time-dependent increases in the Ca2+ signal in the intestine in response to DEC. Application of the TRP channel inhibitor, 2APB, prevented DEC mediated increases in intracellular Ca2+. These observations are important because they emphasize that the nematode intestine, in addition of muscle, is a site of action of DEC as well as other anthelmintics. DEC may also enhance the Ca2+ toxicity effects of other anthelmintics acting on the intestine or, increase the effects of other anthelmintics that are metabolized and excreted by the nematode intestine.
Source: Scientific Reports
Institution: Iowa State University
Language: English
Subfield: Small Animals
Field: Veterinary
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,190
Awards: Slo-1K channels, TRP-2 channels, emodepside and diethylcarbamazine in Filaria, Pharmacological Diversity of nAChRs in Clade III Nematodes: Brugia malayi, Cholinergic anthelmintics: Tachyphylaxis mechanisms and control in a parasitic nematode model,Brugia malayi, Diethylcarbamazine, Emodepside and SLO-1 K Channels of Filaria
OpenAlex ID: W4311679327