The angiotensin converting enzyme inhibitor captopril reduces oviposition and ecdysteroid levels in Lepidoptera

Abstract

The role of angiotensin converting enzyme (ACE, peptidyl dipeptidase A) in metamorphic- and reproductive-related events in the Egyptian cotton leafworm, Spodoptera littoralis (Lepidoptera, Noctuidae) was studied by using the selective ACE inhibitor captopril. Although oral administration of captopril had no effect on larval growth, topical administration to new pupae resulted in a large decrease of successful adult formation. Oviposition and overall appearance of adults emerging from treated larvae did not differ significantly from those emerging from non-treated larvae. In contrast, topical or oral administration of captopril to newly emerged adults caused a reduction in oviposition. By evaluating the effect of captopril on ecdysteroid titers and trypsin activity, we revealed an additional physiological role for ACE. Captopril exerted an inhibitory effect on ecdysteroid levels in female but not in male adults. Larvae fed a diet containing captopril exhibited increased trypsin activity. A similar captopril-induced increase in trypsin activity was observed in female adults. In male adults, however, captopril elicited reduced levels of trypsin activity. Our results suggest that captopril downregulates oviposition by two independent pathways, one through ecdysteroid biosynthesis regulation, and the other through regulation of trypsin activity. Apparently, fecundity is influenced by a complex interaction of ACE, trypsin activity, and ecdysteroid levels.

ACE Inhibitor Captopril Reduces Ecdysteroids and Oviposition in Moths

“…Similarly, when adults were treated with captopril (75 μL; 10 μg/μL) dissolved in the honey‐water diet, a significant reduction in oviposition was also observed. Therefore, we may conclude that captopril can penetrate through the gut epithelium layer as well as through the skin 4. These results are in agreement with those reported for Anopheles stephensi ,2 but are in contrast with the reports concerning the interaction between ACE, ACE inhibitors, and trypsin‐modulating oostatic factor (TMOF) 5…”

The toxicity of angiotensin converting enzyme inhibitors to larvae of the disease vectors Aedes aegypti and Anopheles gambiae

“…This peptidyl dipeptidase is strongly expressed as a glycosylated protein of 72 kDa in several tissues, including male reproductive tissues, the larval and adult midgut, larval trachea and adult salivary gland2627. Other insect species also express ACE in reproductive tissues of both sexes, suggesting a broader physiological role for the enzyme in insect reproduction19282930313233343536. Insect ACE not only resembles the mammalian enzyme in its substrate specificity, but also in susceptibility to inhibitors such as captopril, lisinopril, fosinoprilat, enalapril and trandolaprilat, but apart from captopril these inhibitors can be far less potent towards insect ACE compared to mammalian ACE2223.…”

“…Nevertheless, ACE inhibitors can be acutely toxic to insects, which contrasts with their life-span extending properties in rodents37 and the nematode, Caenorhabditis elegans 38. They have been useful in confirming important roles for ACE in reproduction, growth and development in several insect species30343539. In the mosquito Anopheles stephensi , females fed with ACE inhibitors in the blood meal or females mated with males supplied with ACE inhibitors in their sugar diet, lay significantly fewer eggs than normal323540.…”

Angiotensin-converting enzyme in Spodoptera littoralis: Molecular characterization, expression and activity profile during development

“…The importance of ACE towards a successful metamorphosis is suggested by high ACE activities during last larval stage and early pupal stage in D. melanogaster and Lacanobia oleracea (Siviter et al, 2002b;Ekbote et al, 2003). Evidence from another view, studying the detrimental effect of ACE inhibitors like captopril and fosinopril on growth and development, has been shown for Spodoptera littoralis and Manduca sexta (Vercruysse et al, 2004;Isaac et al, 2007).…”