A Database for Insect Neuropeptide Research

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Insect Neuropeptides - Kinin


(The first members of the kinin family were isolated from extracts of the cockroach Leucophaea maderae using a hindgut contraction assay where the peptides were found to be myostimulatory (Holman et al, 1986; Holman et al, 1987). These eight peptides were designated leucokinin I – VIII (LK-I – VIII). Subsequently kinins have been identified in most insect species (except Coleoptera). The first kinin-encoding gene was cloned from the mosquito Aedes aegypti in 1997 (Veenstra et al, 1997). From this precursor 3 kinin peptides can be cleaved. Ensuing studies have identified precursors with varying numbers of kinin peptides, depending on species. In the blood-sucking bug Rhodnius the precursor encodes 12 copies of kinin (Te Brugge et al, 2011). The active core of the kinins resides in the conserved carboxyterminus pentapeptide FXSWGa (Nachman and Pietrantonio, 2010), and the peptides can vary in length between 6 and 16 residues (Terhzaz et al, 1999). The first kinin receptor (GPCR) was identified from D. melanogaster in 2002 (Radford et al, 2002). Each species analyzed to date appears to have a single kinin receptor.


Kinin peptides were first mapped to neurons and neurosecretory cells in the brains and abdominal ganglia of L. maderae, a few blowfly species and in D. melanogaster and later in other insects (Cantera and Nässel, 1992; Chen et al, 1994; Nässel et al, 1992). In most studied insects kinins are produced in bilateral pairs of neurosecretory cells in segmental abdominal ganglia, and the peptides are likely to serve hormonal functions. Kinins are also produced in CNS interneurons of varying numbers, depending on species (Cantera and Nässel, 1992; Chen et al, 1994; Nässel et al, 1992).


The first identified functions of kinins were myostimulatory activity on visceral and reproductive muscle, as well as stimulation of secretion in renal tubules (Coast et al, 1990; Holman et al, 1987; Schoofs et al, 1993). The mode of action on renal tubules has been extensively studied in several insect species (Dow, 2009; Radford et al, 2002). In D. melanogaster additional functions have been inferred from genetic studies: regulation of sleep, meal size during feeding and a role in desiccation resistance in adult flies (Al-Anzi et al, 2010; Cannell et al, 2016; Liu et al, 2015), and in larvae kinins modulate locomotor behavior and are important in the hormonal cascade triggering ecdysis behavior (Kim et al, 2015; Okusawa et al, 2014; Murakami et al, 2016). Kinins have only been identified in invertebrates, including numerous arthropods, nematodes, annelids and mollusks. Interestingly, a kinin-like receptor has also been identified in Ambulacraria (deuterostomian invertebrates).

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Suggested Reviews

  • Dow JA. 2009. Insights into the Malpighian tubule from functional genomics. J Exp Biol 212(Pt 3):435-445
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  • Halberg KA, Terhzaz S, Cabrero P, Davies SA, Dow JA. Tracing the evolutionary origins of insect renal function. Nat Commun. 2015;6:6800
    View Review
  • Nachman RJ, Pietrantonio PV. 2010. Interaction of mimetic analogs of insect kinin neuropeptides with arthropod receptors. Adv Exp Med Biol 692:27-48.
    View Review
  • Nässel DR, Winther ÅM. 2010. Drosophila neuropeptides in regulation of physiology and behavior. Progr Neurobiol 92(1):42-104.
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  • Al-Anzi, B., Armand, E., Nagamei, P., Olszewski, M., Sapin, V., Waters, C., Zinn, K., Wyman, R.J., and Benzer, S. (2010). The leucokinin pathway and its neurons regulate meal size in Drosophila. Curr Biol 20, 969-978.
  • Cannell, E., Dornan, A.J., Halberg, K.A., Terhzaz, S., Dow, J.A., and Davies, S.A. (2016). The Corticotropin-releasing factor-like diuretic hormone 44 (DH) and kinin neuropeptides modulate desiccation and starvation tolerance in Drosophila melanogaster. Peptides.
  • Cantera, R., and Nässel, D.R. (1992). Segmental peptidergic innervation of abdominal targets in larval and adult dipteran insects revealed with an antiserum against leucokinin I. Cell Tissue Res 269, 459-471.
  • Chen, Y., Veenstra, J.A., Davis, N.T., and Hagedorn, H.H. (1994). A comparative study of leucokinin-immunoreactive neurons in insects. Cell and tissue research 276, 69-83.
  • Clark, L., Agricola, H.J., and Lange, A.B. (2006). Proctolin-like immunoreactivity in the central and peripheral nervous systems of the locust, Locusta migratoria. Peptides 27, 549-558.
  • Coast, G.M., Holman, G.M., and Nachman, R.J. (1990). The diuretic activity of a series of cephalomyotropic neuropeptides, the achetakinins, on isolated Malpighian tubules of the house cricket Acheta domesticus J Insect Physiol 36 481-488.
  • Dow, J.A. (2009). Insights into the Malpighian tubule from functional genomics. J Exp Biol 212, 435-445.
  • Holman, G.M., Cook, B.J., and Nachman, R.J. (1986). Isolation, primary structure and synthesis of two neuropeptides from Leucophaea maderae: members of a new family of cephalotropins. Comp Biochem Physiol 84C 205-211.
  • Holman, G.M., Cook, B.J., and Nachman, R.J. (1987). Isolation, primary structure and synthesis of leukokinins VII and VIII: the final members of this new family of cephalomyotropic peptides isolated from head extracts of Leucophaea maderae. Comp Biochem Physiol 88C, 31-34.
  • Kim, D.H., Han, M.R., Lee, G., Lee, S.S., Kim, Y.J., and Adams, M.E. (2015). Rescheduling Behavioral Subunits of a Fixed Action Pattern by Genetic Manipulation of Peptidergic Signaling. PLoS genetics 11, e1005513. Liu, Y., Luo, J., Carlsson, M.A., and Nässel, D.R. (2015). Serotonin and insulin-like peptides modulate leucokinin-producing neurons that affect feeding and water homeostasis in Drosophila. J Comp Neurol 523, 1840-1863.
  • Murakami K, Yurgel ME, Stahl BA, Masek P, Mehta A, Heidker R, Bollinger W, Gingras RM, Kim YJ, Ja WW, Suter B, DiAngelo JR, Keene AC. 2016. translin Is Required for Metabolic Regulation of Sleep. Curr Biology 26(7):972-980.
  • Nachman, R.J., and Pietrantonio, P.V. (2010). Interaction of mimetic analogs of insect kinin neuropeptides with arthropod receptors. Adv Exp Med Biol 692, 27-48.
  • Nässel, D.R., Cantera, R., and Karlsson, A. (1992). Neurons in the cockroach nervous system reacting with antisera to the neuropeptide leucokinin I. J Comp Neurol 322, 45-67.
  • Okusawa, S., Kohsaka, H., and Nose, A. (2014). Serotonin and downstream leucokinin neurons modulate larval turning behavior in Drosophila. J Neurosci 34, 2544-2558.
  • Radford, J.C., Davies, S.A., and Dow, J.A. (2002). Systematic G-protein-coupled receptor analysis in Drosophila melanogaster identifies a leucokinin receptor with novel roles. J Biol Chem 277, 38810-38817.
  • Schoofs, L., Vanden Broeck, J., and De Loof, A. (1993). The myotropic peptides of Locusta migratoria: structures, distribution, functions and receptors. Insect Biochem Mol Biol 23, 859-881.
  • Terhzaz, S., O'Connell, F. C., Pollock, V. P., Kean, L., Davies, S. A., Veenstra, J. A., & Dow, J. A. (1999). Isolation and characterization of a leucokinin-like peptide of Drosophila melanogaster. Journal of Experimental Biology, 202(24), 3667-3676.
  • Veenstra, J.A., Pattillo, J.M., and Petzel, D.H. (1997). A single cDNA encodes all three Aedes leucokinins, which stimulate both fluid secretion by the malpighian tubules and hindgut contractions. J Biol Chem 272, 10402-10407.