A Database for Insect Neuropeptide Research

Search the database for information about the various species and neuropeptides of interest

Insect Neuropeptides - Pre-ecdysis triggering hormone


Inka cells (or peritracheal cells) were first discovered in Manduca sexta in 1996 (Zitnan et al., 1996). These cells were shown to produce a hormone which acts on the nervous system to trigger ecdysis; this hormone was thus named ecdysis-triggering hormone (ETH). The ETH gene was first cloned in M. sexta followed by the one in Drosophila melanogaster (CG18105) (Park et al., 1999; Zitnan et al., 1999). The ETH precursor in M. sexta encodes two peptides, ETH and pre-ecdysis triggering hormone, PETH) whereas the D. melanogaster precursor encodes two ETH-like peptides (ETH1 and ETH2). The two peptides in both species are functionally different. ETH has a characteristic PRXamide C-terminus. The ETH receptor is homologous to vertebrate neuromedin U receptors (Jékely, 2013). The first ETH receptor (CG5911) was de-orphanized in Drosophila melanogaster (Iversen et al., 2002). Two transcript variants of the receptor are present in D. melanogaster and the receptor variants show differences in ligand sensitivity, cellular distribution and have distinct roles in development (Diao et al., 2016; Park et al., 2003). It might be a similar case in M. sexta where two receptor variants exist (Kim et al., 2006).


Both ETH and PETH are expressed by M. sexta Inka cells (Zitnan et al., 1999). In D. melanogaster, ETH1 and ETH2 are expressed by 18 peritracheal cells that are similar to Inka cells; however, this number is variable in several other species (O’Brien and Taghert, 1998; Zitnan et al., 2003). ETH can be transcriptionally regulated by ecdysone since its promoter contains an ecdysone response element (Park et al., 1999; Zitnan et al., 1999).


In M. sexta, PETH initiates pre-ecdysis I and ETH induces pre-ecdysis II and ecdysis behavior (Zitnan et al., 1999). In Bombyx mori, both peptides induce the entire ecdysis behavioral sequence (Zitnan et al., 2002). Drosophila ETH1 is more potent than ETH2. These peptides play a role in tracheal air filling and the ecdysis sequence (Zitnan et al., 2007).

Suggested Reviews

  • Mesce, K.A., Fahrbach, S.E., 2002. Integration of Endocrine Signals That Regulate Insect Ecdysis. Front. Neuroendocrinol. 23, 179–199. doi:10.1006/frne.2002.0228
    View Review
  • Nässel, D.R., Winther, Å.M.E., 2010. Drosophila neuropeptides in regulation of physiology and behavior. Prog. Neurobiol. 92, 42–104. doi:10.1016/j.pneurobio.2010.04.010
    View Review
  • Žitňan, D., Kim, Y.-J., Žitňanová, I., Roller, L., Adams, M.E., 2007. Complex steroid–peptide–receptor cascade controls insect ecdysis. Gen. Comp. Endocrinol. 153, 88–96. doi:10.1016/j.ygcen.2007.04.002
    View Review


  • Diao, F., Mena, W., Shi, J., Park, D., Diao, F., Taghert, P., Ewer, J., White, B.H., 2016. The Splice Isoforms of the Drosophila Ecdysis Triggering Hormone Receptor Have Developmentally Distinct Roles. Genetics 202, 175–189. doi:10.1534/genetics.115.182121
  • Iversen, A., Cazzamali, G., Williamson, M., Hauser, F., Grimmelikhuijzen, C.J.., 2002. Molecular identification of the first insect ecdysis triggering hormone receptors. Biochem. Biophys. Res. Commun. 299, 924–931. doi:10.1016/S0006-291X(02)02798-5
  • Jékely, G., 2013. Global view of the evolution and diversity of metazoan neuropeptide signalling. Proc. Natl. Acad. Sci. U. S. A. 110, 8702–7. doi:10.1073/pnas.1221833110
  • Kim, Y.-J., Zitnan, D., Cho, K.-H., Schooley, D. a, Mizoguchi, A., Adams, M.E., 2006. Central peptidergic ensembles associated with organization of an innate behavior. Proc. Natl. Acad. Sci. U. S. A. 103, 14211–14216. doi:10.1073/pnas.0603459103
  • O’Brien, M.A., Taghert, P.H., 1998. A peritracheal neuropeptide system in insects: release of myomodulin-like peptides at ecdysis. J. Exp. Biol. 201, 193–209.
  • Park, Y., Kim, Y.-J., Dupriez, V., Adams, M.E., 2003. Two subtypes of ecdysis-triggering hormone receptor in Drosophila melanogaster. J. Biol. Chem. 278, 17710–5. doi:10.1074/jbc.M301119200
  • Park, Y., Zitnan, D., Gill, S.S., Adams, M.E., 1999. Molecular cloning and biological activity of ecdysis-triggering hormones in Drosophila melanogaster. FEBS Lett. 463, 133–138. doi:10.1016/S0014-5793(99)01622-1
  • Zitnan, D., Hollar, L., Spalovská, I., Takác, P., Zitnanová, I., Gill, S.S., Adams, M.E., 2002. Molecular cloning and function of ecdysis-triggering hormones in the silkworm Bombyx mori. J. Exp. Biol. 205, 3459–73. doi:10.1006/bbrc.1996.5915
  • Žitňan, D., Kim, Y.-J., Žitňanová, I., Roller, L., Adams, M.E., 2007. Complex steroid–peptide–receptor cascade controls insect ecdysis. Gen. Comp. Endocrinol. 153, 88–96. doi:10.1016/j.ygcen.2007.04.002
  • Zitnan, D., Ross, L.S., Zitnanova, I., Hermesman, J.L., Gill, S.S., and Adams, M.E. (1999). Steroid induction of a peptide hormone gene leads to orchestration of a defined behavioral sequence. Neuron 23(3), 523-535.doi:10.1016/S0896-6273(00)80805-3
  • Zitnan, D., Zitnanová, I., Spalovská, I., Takác, P., Park, Y., Adams, M.E., 2003. Conservation of ecdysis-triggering hormone signalling in insects. J. Exp. Biol. 206, 1275–89. doi:10.1242/jeb.00261
  • Zitnan, D., Kingan, T.G., Hermesman, J.L., Adams, M.E., 1996. Identification of ecdysis-triggering hormone from an epitracheal endocrine system. Science 271, 88–91. doi:10.1126/science.271.5245.88