A Database for Insect Neuropeptide Research

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Insect Neuropeptides - Diuretic Hormone 44


The first insect diuretic hormone was isolated from 10000 Manduca sexta heads using an in vivo assay (Kataoka et al, 1989). The isolated peptide had considerable sequence similarity with corticotropin-releasing factor (CRF), urotensin-I and sauvagine (a peptide isolated from frog thought to be the amphibian CRF). The peptide comprised 41 amino acid residues and was thus termed Manse-DH41. Afterwards, a shorter peptide (Manse-DH30) was isolated from dissected neuroendocrine cells of brains M. sexta (Blackburn et al, 1991). The first CRF/DH gene was also cloned from M. sexta (Digan et al, 1992). Tribolium castanuem has two CRF/DHs (Trica-DH37 and Trica-DH47) and Bombyx mori has three (Bommo-DH34, Bommo-DH41 and Bommo-DH45) that arise from alternate splicing (Roller et al, 2008). CRF/DH receptors belong to the family of secretin-like GPCRs (subfamily B1). The first CRF/DH receptor was cloned and characterized in M. sexta (Reagan, 1994). This was followed by the cloning and functional expression of Acheta domesticus CRF/DH receptor (Reagan, 1996). In some insects, including Drosophila, there are two CRF/DH receptors that are functionally different (Cardoso et al, 2014; Hector et al, 2009).


CRF/DH expression has been mapped using immunohistochemistry and in situ hybridization in various insects. Within the central nervous system, CRF/DH is expressed in median neurosecretory cells or the brain and lateral neurosecretory cells in the abdominal ganglia (Cabrero et al, 2002; Cannell et al, 2016; Te Brugge et al, 1999; Veenstra and Hagedorn, 1991). The latter cells have also been shown to co-express kinin in some insects (Chen et al, 1994; Te Brugge et al, 2001). CRF-DH-like immunoreactive cells are also found in the gut of few insects (Johard et al, 2003; Wiehart et al, 2002).


The role of insect CRF/DHs in fluid excretion (in vivo and in vitro) has been well established (Cannell et al, 2016; Furuya et al, 2000; Kay et al, 1992; Te Brugge et al, 2011). These peptides also modulate other processes/behaviors besides diuresis. CRF/DHs induces satiety in Schistocerca gregaria and M. sexta (Keeley et al, 1992; Van Wielendele et al, 2012), initiates pre-ecdysis in M. sexta (Kim et al, 2006), retards oocyte growth in S. gregaria (Van Wielendele et al, 2012), modulates normal rest: activity rhythms and control sperm ejection and storage in D. melanogaster (Cavanaugh et al, 2014; Lee et al, 2015).

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Suggested Reviews

  • Nässel, D.R., Winther, Å.M.E., 2010. Drosophila neuropeptides in regulation of physiology and behavior. Prog. Neurobiol. 92, 42–104.
    View Review
  • Schooley, D. A., Horodyski, F.M., Coast, G.M., 2012. Hormones Controlling Homeostasis in Insects, Insect Endocrinology. Elsevier.
    View Review


  • Blackburn, M.B., Kingan, T.G., Bodnar, W., Shabanowitz, J., Hunt, D.F., Kempe, T., Wagner, R.M., Raina, A.K., Schnee, M.E., Ma, M.C., 1991. Isolation and identification of a new diuretic peptide from the tobacco hornworm, Manduca sexta. Biochem. Biophys. Res. Commun. 181, 927–32.
  • Cabrero, P., Radford, J.C., Broderick, K.E., Costes, L., Veenstra, J. a, Spana, E.P., Davies, S. a, Dow, J. a T., 2002. The Dh gene of Drosophila melanogaster encodes a diuretic peptide that acts through cyclic AMP. J. Exp. Biol. 205, 3799–3807.
  • Cannell, E., Dornan, A.J., Halberg, K.A., Terhzaz, S., Dow, J.A.T., Davies, S.-A., 2016. The corticotropin-releasing factor-like diuretic hormone 44 (DH44) and kinin neuropeptides modulate desiccation and starvation tolerance in Drosophila melanogaster. Peptides 44, 1–12.
  • Cardoso, J.C.R., Félix, R.C., Bergqvist, C. a., Larhammar, D., 2014. New insights into the evolution of vertebrate CRH (corticotropin-releasing hormone) and invertebrate DH44 (diuretic hormone 44) receptors in metazoans. Gen. Comp. Endocrinol. 209, 162–170.
  • Cavanaugh, D.J., Geratowski, J.D., Wooltorton, J.R.A., Spaethling, J.M., Hector, C.E., Zheng, X., Johnson, E.C., Eberwine, J.H., Sehgal, A., 2014. Identification of a Circadian Output Circuit for Rest:Activity Rhythms in Drosophila. Cell 157, 689–701.
  • Chen, Y., Veenstra, J.A., Hagedorn, H., Davis, N.T., 1994. Leucokinin and diuretic hormone immunoreactivity of neurons in the tobacco hornworm, Manduca sexta, and co-localization of this immunoreactivity in lateral neurosecretory cells of abdominal ganglia. Cell Tissue Res. 278, 493–507.
  • Digan, M.E., Roberts, D.N., Enderlin, F.E., Woodworth, a R., Kramer, S.J., 1992. Characterization of the precursor for Manduca sexta diuretic hormone Mas-DH. Proc. Natl. Acad. Sci. U. S. A. 89, 11074–8.
  • Furuya, K., Milchak, R.J., Schegg, K.M., Zhang, J., Tobe, S.S., Coast, G.M., Schooley, D. a, 2000. Cockroach diuretic hormones: characterization of a calcitonin-like peptide in insects. Proc. Natl. Acad. Sci. U. S. A. 97, 6469–6474.
  • Hector, C.E., Bretz, C. a, Zhao, Y., Johnson, E.C., 2009. Functional differences between two CRF-related diuretic hormone receptors in Drosophila. J. Exp. Biol. 212, 3142–3147.
  • Johard, H. a D., Coast, G.M., Mordue, W., Nässel, D.R., 2003. Diuretic action of the peptide locustatachykinin I: Cellular localisation and effects on fluid secretion in Malpighian tubules of locusts. Peptides 24, 1571–1579.
  • Kataoka, H., Troetschler, R.G., Li, J.P., Kramer, S.J., Carney, R.L., Schooley, D. a., 1989. Isolation and identification of a diuretic hormone from the tobacco hornworm, Manduca sexta. Proc. Natl. Acad. Sci. U. S. A. 86, 2976–2980.
  • Kay, I., Patel, M., Coast, G.M., Totty, N.F., Mallet, A.I., Goldsworthy, G.J., 1992. Isolation, characterization and biological activity of a CRF-related diuretic peptide from Periplaneta americana L. Regul. Pept. 42, 111–22.
  • Keeley, L.L., Chung, J.S., Hayes, T.K., 1992. Diuretic and antifeedant actions byManduca sexta diuretic hormone in lepidopteran larvae. Experientia 48, 1145–1148.
  • Kim, Y.J., Žitňan, D., Galizia, C.G., Cho, K.H., Adams, M.E., 2006. A Command Chemical Triggers an Innate Behavior by Sequential Activation of Multiple Peptidergic Ensembles. Curr. Biol. 16, 1395–1407.
  • Lee, K.-M., Daubnerová, I., Isaac, R.E., Zhang, C., Choi, S., Chung, J., Kim, Y.-J., 2015. A Neuronal Pathway that Controls Sperm Ejection and Storage in Female Drosophila. Curr. Biol. 25, 790–797.
  • Reagan, J.D., 1996. Molecular cloning and function expression of a diuretic hormone receptor from the house cricket, Acheta domesticus. Insect Biochem. Mol. Biol. 26, 1–6.
  • Reagan, J.D., 1994. Expression cloning of an insect diuretic hormone receptor. A member of the calcitonin/secretin receptor family. J. Biol. Chem. 269, 9–12.
  • Roller, L., Yamanaka, N., Watanabe, K., Daubnerová, I., Žitňan, D., Kataoka, H., Tanaka, Y., 2008. The unique evolution of neuropeptide genes in the silkworm Bombyx mori. Insect Biochem. Mol. Biol. 38, 1147–1157.
  • Te Brugge, V. a, Miksys, S.M., Coast, G.M., Schooley, D. a, Orchard, I., 1999. The distribution of a CRF-like diuretic peptide in the blood-feeding bug Rhodnius prolixus. J. Exp. Biol. 202, 2017–2027.
  • Te Brugge, V. a., Nässel, D.R., Coast, G.M., Schooley, D. a., Orchard, I., 2001. The distribution of a kinin-like peptide and its co-localization with a CRF-like peptide in the blood-feeding bug, Rhodnius prolixus. Peptides 22, 161–173.
  • Te Brugge, V., Paluzzi, J.-P., Schooley, D. a, Orchard, I., 2011. Identification of the elusive peptidergic diuretic hormone in the blood-feeding bug Rhodnius prolixus: a CRF-related peptide. J. Exp. Biol. 214, 371–381.
  • Van Wielendaele, P., Dillen, S., Marchal, E., Badisco, L., Vanden Broeck, J., 2012. CRF-like diuretic hormone negatively affects both feeding and reproduction in the desert locust, Schistocerca gregaria. PLoS One 7.
  • Veenstra, J.A., Hagedorn, H.H., 1991. Identification of neuroendocrine cells producing a diuretic hormone in the tobacco hornworm moth, Manduca sexta. Cell Tissue Res. 266, 359–364.
  • Wiehart, U.I.M., Torfs, P., Van Lommel, A., Nicolson, S.W., Schoofs, L., 2002. Immunocytochemical localization of a diuretic hormone of the beetle Tenebrio molitor, Tenmo-DH(37), in nervous system and midgut. Cell Tissue Res. 308, 421–9.