A Database for Insect Neuropeptide Research

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

Insect Neuropeptides - Crustacean Cardio-Active Peptide


Crustacean cardioactive peptide (CCAP) was first discovered in the shore crab, Carcinus maenas (Stangier et al., 1987). The first insect CCAP was identified in Locusta migratoria (Stangier et al., 1989) and its gene was first discovered in the genome of Drosophila melanogaster (CG4910) and later cloned from Manduca sexta (Hewes and Taghert, 2001; Loi et al., 2001; Vanden Broeck, 2001). Members of the CCAP family in insects are cyclic because they possess two cysteine residues that form an internal disulfide bridge. Thus, the structure of CCAP resembles that of vasopressin/oxytocin peptides; however, they are two distinct peptide families. The first CCAP receptor (CG6111) was de-orphanized in D. melanogaster (Park et al., 2002). Arthropod CCAP receptors are orthologous to vertebrate Neuropeptide S receptors and echinoderm NGFFFamide receptors (Mirabeau and Joly, 2013; Semmens et al., 2015).


CCAP expression has been mapped in several insects including D. melanogaster, L. migratoria , Rhodnius prolixus , M. sexta and Baculum extradentatum (da Silva and Lange, 2006; Draizen et al., 1999; Lange and Patel, 2005; Lee and Lange, 2011; Loi et al., 2001). CCAP is expressed in neurons throughout the nervous system. CCAP is also expressed in the midgut of some insects (Lange and Patel, 2005; Mikani et al., 2015). In D. melanogaster, the majority of the CCAP neurons undergo apoptosis during larval to adult transition (Draizen et al., 1999).


CCAP has multiple functions in insects. Just like in crustaceans, CCAP is cardioactive in several insect species (da Silva et al., 2011; Dulcis et al., 2005, 2001; Lee and Lange, 2011). CCAP also plays an important role in initiating the ecdysis motor program in both holo- and hemi-metabolous insects (Arakane et al., 2008; Gammie and Truman, 1997; Kim et al., 2006a, 2006b; Lee et al., 2013). In addition, CCAP stimulates alpha-amylase and protease activities in the midgut of P. americana (Matsui et al., 2013) and stimulates contractions of tissues such as the hindgut and oviduct (Donini et al., 2001; Lee and Lange, 2011).

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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. doi:10.1016/j.pneurobio.2010.04.010
    View Review
  • Valsalan, R., Manoj, N., 2014. Evolutionary history of the neuropeptide S receptor/neuropeptide S system. Gen. Comp. Endocrinol. 209, 11–20. doi:10.1016/j.ygcen.2014.05.011
    View Review


  • Arakane, Y., Li, B., Muthukrishnan, S., Beeman, R.W., Kramer, K.J., Park, Y., 2008. Functional analysis of four neuropeptides, EH, ETH, CCAP and bursicon, and their receptors in adult ecdysis behavior of the red flour beetle, Tribolium castaneum. Mech. Dev. 125, 984–95. doi:10.1016/j.mod.2008.09.002
  • da Silva, R., Lange, A.B., 2006. The association of crustacean cardioactive peptide with the spermatheca of the African migratory locust, Locusta migratoria. J. Insect Physiol. 52, 399–409. doi:10.1016/j.jinsphys.2006.01.006
  • da Silva, S.R., Silva, R. Da, Lange, A.B., 2011. Effects of crustacean cardioactive peptide on the hearts of two Orthopteran insects, and the demonstration of a Frank-Starling-like effect. Gen. Comp. Endocrinol. 171, 218–224. doi:10.1016/j.ygcen.2011.01.015
  • Donini, Agricola, Lange, 2001. Crustacean cardioactive peptide is a modulator of oviduct contractions in Locusta migratoria. J. Insect Physiol. 47, 277–285.
  • Draizen, T.A., Ewer, J., Robinow, S., 1999. Genetic and hormonal regulation of the death of peptidergic neurons in the Drosophila central nervous system. J. Neurobiol. 38, 455–65.
  • Dulcis, D., Davis, N.T., Hildebrand, J.G., 2001. Neuronal control of heart reversal in the hawkmoth Manduca sexta. J. Comp. Physiol. A. 187, 837–49.
  • Dulcis, D., Levine, R.B., Ewer, J., 2005. Role of the neuropeptide CCAP in Drosophila cardiac function. J. Neurobiol. 64, 259–74. doi:10.1002/neu.20136
  • Gammie, S.C., Truman, J.W., 1997. Neuropeptide hierarchies and the activation of sequential motor behaviors in the hawkmoth, Manduca sexta. J. Neurosci. 17, 4389–97.
  • Hewes, R.S., Taghert, P.H., 2001. Neuropeptides and neuropeptide receptors in the Drosophila melanogaster genome. Genome Res. 11, 1126–1142. doi:10.1101/gr.169901
  • Kim, Y.J., Zitnan, D., Cho, K.-H., Schooley, D. a, Mizoguchi, A., Adams, M.E., 2006a. 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
  • Kim, Y.J., Žitňan, D., Galizia, C.G., Cho, K.H., Adams, M.E., ??it??an, D., Galizia, C.G., Cho, K.H., Adams, M.E., 2006b. A Command Chemical Triggers an Innate Behavior by Sequential Activation of Multiple Peptidergic Ensembles. Curr. Biol. 16, 1395–1407. doi:10.1016/j.cub.2006.06.027
  • Lange, A.B., Patel, K., 2005. The presence and distribution of crustacean cardioactive peptide in the central and peripheral nervous system of the stick insect, Baculum extradentatum. Regul. Pept. 129, 191–201. doi:10.1016/j.regpep.2005.02.011
  • Lee, D., Orchard, I., Lange, A.B., 2013. Evidence for a conserved CCAP-signalling pathway controlling ecdysis in a hemimetabolous insect, Rhodnius prolixus . Front. Neurosci. doi:10.3389/fnins.2013.00207
  • Lee, D.H., Lange, A.B., 2011. Crustacean cardioactive peptide in the Chagas’ disease vector, Rhodnius prolixus : Presence, distribution and physiological effects. Gen. Comp. Endocrinol. 174, 36–43. doi:10.1016/j.ygcen.2011.08.007
  • Loi, P.K., Emmal, S.A., Park, Y., Tublitz, N.J., 2001. Identification, sequence and expression of a crustacean cardioactive peptide (CCAP) gene in the moth Manduca sexta. J. Exp. Biol. 204, 2803–16.
  • Matsui, T., Sakai, T., Satake, H., Takeda, M., 2013. The pars intercerebralis affects digestive activities of the American cockroach, Periplaneta americana, via crustacean cardioactive peptide and allatostatin-A. J. Insect Physiol. 59, 33–37. doi:10.1016/j.jinsphys.2012.06.010
  • Mikani, A., Watari, Y., Takeda, M., 2015. Brain-midgut cross-talk and autocrine metabolastat via the sNPF/CCAP negative feed-back loop in the American cockroach, Periplaneta americana. Cell Tissue Res. 362, 481–96. doi:10.1007/s00441-015-2242-4
  • Mirabeau, O., Joly, J.-S., 2013. Molecular evolution of peptidergic signalling systems in bilaterians. Proc. Natl. Acad. Sci. U. S. A. 110, E2028-37. doi:10.1073/pnas.1219956110
  • Park, Y., Kim, Y.-J., Adams, M.E., 2002. Identification of G protein-coupled receptors for Drosophila PRXamide peptides, CCAP, corazonin, and AKH supports a theory of ligand-receptor coevolution. Proc. Natl. Acad. Sci. U. S. A. 99, 11423–11428. doi:10.1073/pnas.162276199
  • Semmens, D.C., Beets, I., Rowe, M.L., Blowes, L.M., Oliveri, P., Elphick, M.R., 2015. Discovery of sea urchin NGFFFamide receptor unites a bilaterian neuropeptide family. Open Biol.
  • Stangier, J., Hilbich, C., Beyreuther, K., Keller, R., 1987. Unusual cardioactive peptide (CCAP) from pericardial organs of the shore crab Carcinus maenas . Proc. Natl. Acad. Sci. U. S. A. 84, 575.
  • Stangier, J., Hilbich, C., Keller, R., 1989. Occurrence of crustacean cardioactive peptide (CCAP) in the nervous system of an insect,Locusta migratoria. J. Comp. Physiol. B 159, 5–11. doi:10.1007/BF00692677
  • Vanden Broeck, J., 2001. Neuropeptides and their precursors in the fruitfly, Drosophila melanogaster. Peptides 22, 241–54.