A Database for Insect Neuropeptide Research

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

Insect Neuropeptides - FMRFamide


The first member of the FMRFamide family was isolated and sequenced from the clam Macrocallista nimbosa based on its cardio-excitatory properties (Price and Greenberg, 1977). They were named based on their characteristic FMRFamide C-terminal sequence. The gene encoding FMRFamide was first cloned in Drosophila melanogaster (CG2346) (Nambu et al., 1988; Schneider and Taghert, 1988). This was the first insect neuropeptide gene to be cloned. The FMRFamide gene encodes multiple peptides and their number varies between species (Wegener and Gorbashov, 2008). The first insect FMRFamide receptor was de-orphanized in D. melanogaster (CG2114) by two independent studies (Cazzamali and Grimmelikhuijzen, 2002; Meeusen et al., 2002). In the past, FMRFamides were grouped along with other peptides families that also possess the C-terminal FMRFamide sequence (or its variations). These include myosuppressins, NPF, sNPF and sulfakinin and were collectively referred to as FMRFamide-related peptides (FaRPs). However, it is now clear that these are all independent peptide families and act on their specific receptors (Jékely, 2013; Mirabeau and Joly, 2013).


FMRFamide-like immunohistochemistry has been examined in members of almost all animal phyla. However, due to the sequence similarity between ‘true’ FMRFamides and other FaRPs, immuno-histochemical studies must be treated with caution. FMRFamide expression has been localized using in situ hybridization in D. melanogaster and Musca domestica, (Matsushima et al., 2007; O’Brien et al., 1991). FMRFamide is expressed in the brain and in three pairs of neurosecretory cells in the ventral nerve cord of D. melanogaster.


FMRFamides are pleiotropic and thus participate in various processes. They are myostimulatory on various muscle in several insect species (Lange and Cheung, 1999; Ormerod et al., 2015; Sedra and Lange, 2014; Suggs et al., 2016). In Calliphora vomitoria, FMRFamides induce fluid secretion from salivary glands (Duve et al., 1992), whereas in D. melanogaster, FMRFamide plays a part in the ecdysis behavior (Kim et al., 2006) and promotes stress-induced sleep (Lenz et al., 2015).

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Suggested Reviews

  • Nässel, D.R., Winther, Å.M.E., 2010. Drosophila neuropeptides in regulation of physiology and behaviour. Prog. Neurobiol. 92, 42–104. doi:10.1016/j.pneurobio.2010.04.010
    View Review
  • Nichols, R., 2003. Signalling pathways and physiological functions of Drosophila melanogaster FMRFamide-related peptides. Annu. Rev. Entomol. 48, 485–503. doi:10.1146/annurev.ento.48.091801.112525
    View Review
  • Orchard, I., Lange, A.B., and Bendena, W.G. (2001). FMRFamide-related peptides: a multifunctional family of structurally related neuropeptides in insects. Adv Insect Physiol 28, 267-329.
    View Review
  • Walker, R.J., Papaioannou, S., and Holden-Dye, L. (2009). A review of FMRFamide- and RFamide-like peptides in metazoa. Invertebrate neuroscience : IN 9(3-4), 111-153. doi: 10.1007/s10158-010-0097-7.
    View Review


  • Cazzamali, G., Grimmelikhuijzen, C.J.P., 2002. Molecular cloning and functional expression of the first insect FMRFamide receptor. Proc. Natl. Acad. Sci. U. S. A. 99, 12073–8. doi:10.1073/pnas.192442799
  • Duve, H., Johnsen, A.H., Sewell, J.C., Scott, A.G., Orchard, I., Rehfeld, J.F., Thorpe, A., 1992. Isolation, structure, and activity of -Phe-Met-Arg-Phe-NH2 neuropeptides (designated calliFMRFamides) from the blowfly Calliphora vomitoria. Proc. Natl. Acad. Sci. U. S. A. 89, 2326–30.
  • 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., Žitňan, D., Galizia, C.G., Cho, K.H., Adams, M.E., ??it??an, D., Galizia, C.G., Cho, K.H., Adams, M.E., 2006. A Command Chemical Triggers an Innate Behaviour by Sequential Activation of Multiple Peptidergic Ensembles. Curr. Biol. 16, 1395–1407. doi:10.1016/j.cub.2006.06.027
  • Lange, A.B., Cheung, I.L., 1999. The modulation of skeletal muscle contraction by FMRFamide-related peptides of the locust. Peptides 20, 1411–8.
  • Lenz, O., Xiong, J., Nelson, M.D., Raizen, D.M., Williams, J.A., 2015. FMRFamide signalling promotes stress-induced sleep in Drosophila. Brain. Behav. Immun. 47, 141–8. doi:10.1016/j.bbi.2014.12.028
  • Matsushima, A., Takano, K., Yoshida, T., Takeda, Y., Yokotani, S., Shimohigashi, Y., Shimohigashi, M., 2007. Double-labelled in situ hybridization reveals the lack of co-localization of mRNAs for the circadian neuropeptide PDF and FMRFamide in brains of the flies Musca domestica and Drosophila melanogaster. J. Biochem. 141, 867–77. doi:10.1093/jb/mvm094
  • Meeusen, T., Mertens, I., Clynen, E., Baggerman, G., Nichols, R., Nachman, R.J., Huybrechts, R., De Loof, A., Schoofs, L., 2002. Identification in Drosophila melanogaster of the invertebrate G protein-coupled FMRFamide receptor. Proc. Natl. Acad. Sci. U. S. A. 99, 15363–8. doi:10.1073/pnas.252339599
  • 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
  • Nambu, J.R., Murphy-Erdosh, C., Andrews, P.C., Feistner, G.J., Scheller, R.H., 1988. Isolation and characterization of a Drosophila neuropeptide gene. Neuron 1, 55–61.
  • O’Brien, M.A., Schneider, L.E., Taghert, P.H., 1991. In situ hybridization analysis of the FMRFamide neuropeptide gene in Drosophila. II. Constancy in the cellular pattern of expression during metamorphosis. J. Comp. Neurol. 304, 623–38. doi:10.1002/cne.903040409
  • Ormerod, K.G., Krans, J.L., Mercier, A.J., 2015. Cell-selective modulation of the Drosophila neuromuscular system by a neuropeptide. J. Neurophysiol. 113, 1631–43. doi:10.1152/jn.00625.2014
  • Price, D.A., Greenberg, M.J., 1977. Structure of a molluscan cardioexcitatory neuropeptide. Science 197, 670–1.
  • Schneider, L.E., Taghert, P.H., 1988. Isolation and characterization of a Drosophila gene that encodes multiple neuropeptides related to Phe-Met-Arg-Phe-NH2 (FMRFamide). Proc. Natl. Acad. Sci. U. S. A. 85, 1993–7.
  • Sedra, L., Lange, A.B., 2014. The female reproductive system of the kissing bug, Rhodnius prolixus : arrangements of muscles, distribution and myoactivity of two endogenous FMRFamide-like peptides. Peptides 53, 140–7. doi:10.1016/j.peptides.2013.04.003
  • Suggs, J.M., Jones, T.H., Murphree, S.C., Hillyer, J.F., 2016. CCAP and FMRFamide-like peptides accelerate the contraction rate of the antennal accessory pulsatile organs (auxiliary hearts) of mosquitoes. J. Exp. Biol. 219, 2388–95. doi:10.1242/jeb.141655
  • Wegener, C., Gorbashov, A., 2008. Molecular evolution of neuropeptides in the genus Drosophila. Genome Biol. 9, R131. doi:10.1186/gb-2008-9-8-r131