A Database for Insect Neuropeptide Research

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

Insect Neuropeptides - Diuretic Hormone 31


The first member of the DH31 family was isolated from brains of the cockroach Diploptera punctata using a Malpighian tubule (MT) secretion assay (Furuya et al, 2000). The isolated peptide was 31 amino acids long and stimulated secretion by MTs, and was thus named DH31. A manual search of a peptide catalog revealed that the isolated peptide shared the Pro-amide C-terminus with the vertebrate calcitonin. However, DH31 lacks the disulfide bridge that is present in vertebrate calcitonin. The ability of vertebrate calcitonin to stimulate secretion by insect MTs strengthened the relationship between DH31 and calcitonin. Although there is not much sequence similarity between calcitonin and DH31, the length of the peptide appears to be conserved throughout animal evolution and is critical for its function (Zandawala et al, 2015). The first gene encoding DH31 was discovered from the genome of Drosophila melanogaster (Coast et al, 2001). Since then, DH31 has been identified in transcriptomes and genomes of several species belonging to Arthropoda, Nematoda and Lophotrochozoa (Mirabeau and Joly, 2013; Zandawala, 2012). The first DH31 receptor (Family B GPCR) was deorphanized from D. melanogaster in 2005 (Johnson et al, 2005). More recently, another study deorphanized two DH31 receptors in the kissing bug, Rhodnius prolixus and showed that most insects, including D. melanogaster possess two DH31 receptors (Zandawala et al, 2013).


DH31 has been localized to neurons and neurosecretory cells in the brain and abdominal ganglia of several insects (Park et al, 2008; Te Brugge and Orchard, 2008; Te Brugge et al, 2005). DH31 is also expressed in enteroendocrine cells of the D. melanogaster and Oncopeltus fasciatus midgut, but not in R. prolixus midgut (Te Brugge and Orchard, 2008; Veenstra, 2009; Veenstra et al, 2008). DH31-expressing enteroendocrine cells of the D. melanogaster midgut have recently been shown to be activated following ingestion of amino acid or protein-rich diet (Park et al, 2016).


Aside from its role in fluid secretion in MTs, DH31 causes contractions of various muscle types (hindgut, midgut and salivary glands) in several insects (Brugge et al, 2008; LaJeunesse et al, 2010; Orchard, 2009). DH31 signaling also plays a role in male courtship and circadian control of sleep in D. melanogaster (Kunst et al, 2014; Li et al, 2011). The presence of DH31 in neurons expressing the ecdysis triggering hormone (ETH) receptor in Manduca sexta suggests that it could be one of the peptides modulating ecdysis behavior (Kim et al, 2004).

SeqLogo and Cladogram

Click above image to go to SeqLogo and Cladogram page

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
  • Zandawala, M., 2012. Calcitonin-like diuretic hormones in insects. Insect Biochem. Mol. Biol. 42, 816–25.
    View Review


  • Brugge, V. a Te, Schooley, D. a, Orchard, I., 2008. Amino acid sequence and biological activity of a calcitonin-like diuretic hormone (DH31) from Rhodnius prolixus. J. Exp. Biol. 211, 382–390.
  • Coast, G.M., Webster, S.G., Schegg, K.M., Tobe, S.S., Schooley, D. a, 2001. The Drosophila melanogaster homologue of an insect calcitonin-like diuretic peptide stimulates V-ATPase activity in fruit fly Malpighian tubules. J. Exp. Biol. 204, 1795–1804.
  • 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.
  • Johnson, E.C., Shafer, O.T., Trigg, J.S., Park, J., Schooley, D. a, Dow, J. a, Taghert, P.H., 2005. A novel diuretic hormone receptor in Drosophila: evidence for conservation of CGRP signaling. J. Exp. Biol. 208, 1239–1246.
  • Kim, Y.-J., Spalovská-Valachová, I., Cho, K.-H., Zitnanova, I., Park, Y., Adams, M.E., Zitnan, D., 2004. Corazonin receptor signaling in ecdysis initiation. Proc. Natl. Acad. Sci. U. S. A. 101, 6704–6709.
  • Kunst, M., Hughes, M.E., Raccuglia, D., Felix, M., Li, M., Barnett, G., Duah, J., Nitabach, M.N., 2014. Calcitonin gene-related peptide neurons mediate sleep-specific circadian output in Drosophila. Curr. Biol. 24, 2652–2664.
  • LaJeunesse, D.R., Johnson, B., Presnell, J.S., Catignas, K.K., Zapotoczny, G., 2010. Peristalsis in the junction region of the Drosophila larval midgut is modulated by DH31 expressing enteroendocrine cells. BMC Physiol. 10, 14.
  • Li, Y., Hoxha, V., Lama, C., Dinh, B.H., Vo, C.N., Dauwalder, B., 2011. The hector G-protein coupled receptor is required in a subset of fruitless neurons for male courtship behavior. PLoS One 6.
  • Mirabeau, O., Joly, J.-S., 2013. Molecular evolution of peptidergic signaling systems in bilaterians. Proc. Natl. Acad. Sci. U. S. A. 110, E2028–37.
  • Orchard, I., 2009. Peptides and serotonin control feeding-related events in Rhodnius prolixus. Front. Biosci. 250–262.
  • Park, D., Veenstra, J. a., Park, J.H., Taghert, P.H., 2008. Mapping peptidergic cells in Drosophila: Where DIMM fits in. PLoS One 3.
  • Park, J.-H., Chen, J., Jang, S., Ahn, T.J., Kang, K., Choi, M.S., Kwon, J.Y., 2016. A subset of enteroendocrine cells is activated by amino acids in the Drosophila midgut. FEBS Lett. 590, 493–500.
  • Te Brugge, V. a., Lombardi, V.C., Schooley, D. a., Orchard, I., 2005. Presence and activity of a Dippu-DH 31-like peptide in the blood-feeding bug, Rhodnius prolixus. Peptides 26, 29–42.
  • Te Brugge, V. a., Orchard, I., 2008. Distribution and activity of a Dippu DH31-like peptide in the large milkweed bug Oncopeltus fasciatus. Peptides 29, 206–213.
  • Veenstra, J. a., 2009. Peptidergic paracrine and endocrine cells in the midgut of the fruit fly maggot. Cell Tissue Res. 336, 309–323.
  • Veenstra, J. a., Agricola, H.J., Sellami, A., 2008. Regulatory peptides in fruit fly midgut. Cell Tissue Res. 334, 499–516.
  • Zandawala, M., 2012. Calcitonin-like diuretic hormones in insects. Insect Biochem. Mol. Biol. 42, 816–25.
  • Zandawala, M., Li, S., Hauser, F., Grimmelikhuijzen, C.J.P., Orchard, I., 2013. Isolation and functional characterization of calcitonin-like diuretic hormone receptors in Rhodnius prolixus. PLoS One 8, e82466.
  • Zandawala, M., Poulos, C., Orchard, I., 2015. Structure-activity relationships of two Rhodnius prolixus calcitonin-like diuretic hormone analogs. Peptides 68, 211–213.