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Neuropeptide Systems as Targets for Parasite and Pest Control pp 10–26Cite as

Nonpeptide Ligands for Peptidergic G Protein-Coupled Receptors

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Part of the book series: Advances in Experimental Medicine and Biology ((volume 692))

Abstract

Neuropeptides play essential roles in many physiological systems in vertebrates and invertebrates. Peptides per se are difficult to use as therapeutic agents, as they are generally very unstable in biological fluid environments and cross biological membranes poorly. Recognition that nonpeptide ligands for peptide receptors have clinical utility came from the discovery that opiates (such as morphine) act by binding to G protein-coupled receptors (GPCRs) for which the endogenous ligands are a family of neuropeptides (enkephalins and endorphins). Basic research has revealed a very large number of distinct neuropeptides that influence virtually every aspect of mammalian physiology and considerable effort has been expended in the pursuit of new drugs that act through peptidergic signaling systems. Although useful drugs have been found to affect various aspects of neuropeptide biology, most work has been devoted to the discovery of nonpeptide ligands that act as agonists or antagonists at peptidergic GPCRs. Similar opportunities are apparent for the discovery of nonpeptide ligands that act on invertebrate GPCRs. A consideration of the knowledge gained from the process as conducted for mammalian peptidergic systems can inform and illuminate promising strategies for the discovery of new drugs for the treatment and control of pests and parasites.

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References

  1. Scharrer B. The neuropeptide saga. Amer Zool 1990; 30:887–95.

    CAS  Google Scholar 

  2. Hökfelt T, Broberge C, Xu ZQD et al. Neuropeptides—an overview. Neuropharmacol 2000; 39:1337–56.

    Article  Google Scholar 

  3. Strand FL. Neuropeptides: Regulators of Physiological Processes. MIT Press, Cambridge, MA 1999.

    Google Scholar 

  4. Hökfelt T, Bartfai T, Bloom F. Neuropeptides: opportunities for drug discovery. Lancet Neurol 2003; 2:463–72.

    Article  PubMed  Google Scholar 

  5. Brain SD, Cox HM. Neuropeptides and their receptors: innovative science providing novel therapeutic targets. Brit J Pharmacol 2006; 147:S202–11.

    Article  CAS  Google Scholar 

  6. Nässel DR. Neuropeptides in the nervous system of Drosophila and other insects: multiple roles as neuromodulators and neurohormones. Prog Neurobiol 2002; 68:1–84.

    Article  PubMed  Google Scholar 

  7. McVeigh P, Kimber MJ, Novozhilova E et al. Neuropeptide signaling systems in flatworms. Parasitol 2005; 131(Suppl):S41–55.

    CAS  Google Scholar 

  8. McVeigh P, Leech S, Mair GR et al. Analysis of FMRFamide-like peptide (FLP) diversity in phylum Nematoda. Int J Parasitol 2005; 35:1043–60.

    Article  CAS  PubMed  Google Scholar 

  9. McVeigh P, Alexander-Bowman S, Veal E et al. Neuropeptide-like protein diversity in phylum Nematoda. Int J Parasitol 2008; 38:1493–503.

    Article  CAS  Google Scholar 

  10. Masler EP, Kelly TJ, Menn JJ. Insect neuropeptides: discovery and application in insect management. Arch Insect Biochem Physiol 1993; 22:87–111.

    Article  CAS  PubMed  Google Scholar 

  11. Gäde G, Goldsworthy GJ. Insect peptide hormones: a selective review of their physiology and potential application for pest control. Pest Man Sci 2003; 59:1063–75.

    Article  CAS  Google Scholar 

  12. Maule AG, Mousley A, Marks NJ et al. Neuropeptide signaling systems—potential targets for parasite and pest control. Curr Top Med Chem 2002; 2:733–58.

    Article  CAS  PubMed  Google Scholar 

  13. Mousley A, Maule AG, Halton DW et al. Inter-phyla studies on neuropeptides: the potential for broad-spectrum anthelmintic and/or endectocide discovery. Parasitol 2005; 131(Suppl):S143–67.

    CAS  Google Scholar 

  14. Greenwood K, Williams T, Geary T. Nematode neuropeptide receptors and their development as anthelmintic screens. Parasitol 2005; 131:S169–77.

    Article  CAS  Google Scholar 

  15. Åkerlund M. Oxytocin antagonists in the treatment of preterm labour. Fet Matern Med Rev 2002; 13:31–41.

    Article  Google Scholar 

  16. Ashworth DM, Bit AR, Baxter AJ et al. Nonpeptide oxytocin agonists. Drugs Future 2006; 31:345–53.

    Article  CAS  Google Scholar 

  17. Lottmann H, Baydala L, Eggert P et al. Long-term desmopressin response in primary nocturnal enuresis: open-label, multinational study. Int J Clin Pract 2009; 63:35–45.

    Article  CAS  PubMed  Google Scholar 

  18. Decaux G, Soupart A, Vassart G. Nonpeptide arginine-vasopressin antagonists: the vaptans. Lancet 2008; 371:1624–32.

    Article  CAS  PubMed  Google Scholar 

  19. Matchar DB, McCrory DC, Orlando LA et al. Systematic review: comparative effectiveness of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers for treating essential hypertension. Ann Intern Med 2008; 148:16–29.

    PubMed  Google Scholar 

  20. Ram CV. Angiotensin receptor blockers: current status and future prospects. Am J Med 2008; 121:656–63.

    Article  CAS  PubMed  Google Scholar 

  21. Zerilli T, Pyon EY. Sitagliptin phosphate: a DPP-4 inhibitor for the treatment of type 2 diabetes mellitus. Clin Ther 2007; 29:2614–34.

    Article  CAS  PubMed  Google Scholar 

  22. Knop FK, Vilsbøll, T, Holst JJ. Incretin-based therapy of type 2 diabetes mellitus. Curr Prot Pept Sci 2009; 10:46–55.

    Article  CAS  Google Scholar 

  23. Hansen KB, Knop FK, Holst JJ et al. Treatment of type 2 diabetes with glucagon-like peptide-1 receptor agonists. Int J Clin Pract 2009; 63:1154–60.

    Article  CAS  PubMed  Google Scholar 

  24. Jones RM, Boatman PD, Semple G et al. Clinically validated peptides as templates for de novo peptidomimetic drug design as G-protein-coupled receptors. Curr Opin Pharmacol 2003; 3:530–543.

    Article  CAS  PubMed  Google Scholar 

  25. Lingueglia E, Deval E, Lazdunski M. FMRFamide-gated sodium channel and ASIC channels: a new class of ionotropic receptors for FMRFamide and related peptides. Peptides 2006; 27:1138–52.

    Article  CAS  PubMed  Google Scholar 

  26. Purcell J, Robertson AP, Thompson DP et al. PF4, a FMRFamide-related peptide, gates low-conductance Cl− channels in Ascaris suum. Eur J Pharmacol 2002; 456:11–17.

    Article  CAS  PubMed  Google Scholar 

  27. Meeusen T, Mertens I, De Loof A et al. G protein-coupled receptors in invertebrates: a state of the art. Int Rev Cytol 2003; 230:189–261.

    Article  CAS  PubMed  Google Scholar 

  28. Claeys I, Poels J, Simonet G et al. Insect neuropeptide and peptide hormone receptors: current knowledge and future directions. Vit Horm 2005; 73:217–86.

    Article  CAS  Google Scholar 

  29. Hawking F. History of chemotherapy. In: Schnitze RJ, Hawking F, eds. Experimental Chemotherapy. New York: Academic Press, 1963:1–24.

    Google Scholar 

  30. Drews J. Drug discovery: a historical perspective. Science 2000; 287:1960–63.

    Article  CAS  PubMed  Google Scholar 

  31. Williams M. Receptor binding in the drug discovery process. Med Res Rev 1991; 11:147–184.

    CAS  PubMed  Google Scholar 

  32. Kenny BA, Bushfield M, Parry-Smith DJ et al. The application of high-throughput screening to novel lead discovery. Prog Drug Res 1988; 51:245–269.

    Google Scholar 

  33. Hughes J, Smith T, Kosterlitz H et al. Isolation of two related pentapeptides from the brain with potent opiate agonist activity. Nature 1975; 258:577–9.

    Article  CAS  PubMed  Google Scholar 

  34. Janecka A, Fichna J, Janecki T. Opioid receptors and their ligands. Curr Top Med Chem 2004; 4:1–17.

    Article  CAS  PubMed  Google Scholar 

  35. Snyder SH, Pasternak GW. Historical review: opioid receptors. Trends Pharmacol Sci 2003; 24:198–205.

    Article  CAS  PubMed  Google Scholar 

  36. Chang RSL, Lotti VJ, Monaghan RL et al. A potent nonpeptide cholecystokinin antagonist selective for peripheral tissues isolated from Aspergillus alliaceus. Science 1985; 230:177–9.

    Article  CAS  PubMed  Google Scholar 

  37. Evans BE, Rittle KE, Bock MG et al. Methods for drug discovery: development of potent, selective, orally effective cholecystokinin antagonists. J Med Chem 1988; 31:2235–46.

    Article  CAS  PubMed  Google Scholar 

  38. Goldstein A, Lowney LI, Pal BK. Stereospecific and nonspecific interactions of the morphine congener levorphanol in subcellular fractions of mouse brain. Proc Natl Acad Sci USA 1971; 68:1742–47.

    Article  CAS  PubMed  Google Scholar 

  39. Cooke D, Bloom S. The obesity pipeline: current strategies in the development of anti-obesity drugs. Nature Revs Drug Disc 2006; 5:919–31.

    Article  CAS  Google Scholar 

  40. Herranz R. Cholecystokinin antagonists: pharmacological and therapeutic potential. Med Res Rev 2003; 23:559–605.

    Article  CAS  PubMed  Google Scholar 

  41. Berna MJ, Tapia JA, Sancho V et al. Progress in developing cholecystokinin (CCK)/gastrin receptor ligands that have therapeutic potential. Curr Opin Pharmacol 2007; 7:583–92.

    Article  CAS  PubMed  Google Scholar 

  42. Silverman L, Campbell R, Broach JR. New assay technologies for high-throughput screening. Curr Opin Chem Biol 1998; 2:397–403.

    Article  CAS  PubMed  Google Scholar 

  43. Pausch MH. G protein-coupled receptors in Saccharomyces cerevisiae: high-throughput screening assays for drug discovery. Trends Biotech 1997; 15:487–94.

    Article  CAS  Google Scholar 

  44. Dowell SJ, Brown AJ. Yeast assays for G protein-coupled receptors. Receptors Channels 2002; 8:343–52.

    Article  CAS  PubMed  Google Scholar 

  45. Thomsen W, Frazer J, Unett D. Functional assays for screening GPCR targets. Curr Opin Biotech 2005; 16:655–65.

    CAS  PubMed  Google Scholar 

  46. Wang ZX, Broach JR, Peiper SC. Functional expression of CXCR4 in Saccharomyces cerevisiae in the development of powerful tools for the pharmacological characterization of CXCR4. (2006) Meth Mol Biol 2006; 332:115–27.

    Google Scholar 

  47. Berthold M, Bartfai T. Modes of peptide binding in G protein-coupled receptors. Neurochem Res 1997; 22:1023–31.

    Article  CAS  PubMed  Google Scholar 

  48. Snider RM, Constantine JW, Lowe JA III et al. A potent nonpeptide antagonist of the Substance P (NK1) receptor. Science 1991; 251:435–7.

    Article  CAS  PubMed  Google Scholar 

  49. Gether U, Johansen TE, Snider RM et al. Different binding epitopes on the NK1 receptor for substance P and a nonpeptide antagonist. Nature 1993; 362:345–8.

    Article  CAS  PubMed  Google Scholar 

  50. Fong TM, Cascieri MA, Yu H et al. Amino-aromatic interaction between histidine 197 of the neurokinin-1 receptor and CP 96345. Nature 1993; 362:350–3.

    Article  CAS  PubMed  Google Scholar 

  51. Fong TM, Yu H, Strader CD. Molecular basis for the species-selectivity of the Neurokinin-1 receptor antagonists CP-96,345 and RP67580. J Biol Chem 1992; 267:25668–71.

    CAS  PubMed  Google Scholar 

  52. Sachais BS, Snider RM, Lowe JA III et al. Molecular basis for the species selectivity of the Substance P antagonist CP-96,345. J Biol Chem 1993; 268:2319–23.

    CAS  PubMed  Google Scholar 

  53. Garret C, Carruette A, Fardin V et al. Pharmacological properties of a potent and selective nonpeptide substance P antagonist. Proc Natl Acad Sci USA 1991; 88:10208–12.

    Article  CAS  PubMed  Google Scholar 

  54. Beinborn M, Lee YM, McBride EW et al. A single amino acid of the cholecystokinin-B/gastrin receptor determines specificity for nonpeptide antagonists. Nature 1993; 362:348–50.

    Article  CAS  PubMed  Google Scholar 

  55. Satoh M, Minami M. Molecular pharmacology of the opioid receptors. Pharmacol Ther 1995; 68:343–64.

    Article  CAS  PubMed  Google Scholar 

  56. Michel MC, Beck-Sickinger A, Cox H et al. XVI. International union of pharmacology recommendations for the nomenclature of neuropeptide Y, peptide YY and pancreatic polypeptide receptors. Pharmacol Rev 1998; 50:143–50.

    CAS  PubMed  Google Scholar 

  57. Sugg EE. Nonpeptide agonists for peptide receptors: lessons from ligands. Ann Rep Med Chem 1997; 32:277–83.

    Article  CAS  Google Scholar 

  58. Marshall GR. Peptide interactions with G-protein coupled receptors. Biopolymers 2001; 60:246–77.

    Article  CAS  PubMed  Google Scholar 

  59. Giannis A, Kolter T. Peptidomimetics for receptor ligands—discovery, development and medical perspectives. Agnew Chem Int Ed Engl 1993; 32:1244–67.

    Article  Google Scholar 

  60. Hruby VY, Agnes RS. Conformation-activity relationships of opioid peptides with selective activities at opiate receptors. Biopolymers 1999; 51:391–410.

    Article  CAS  PubMed  Google Scholar 

  61. Rashid AJ, O’Dowd BF, George SN. Minireview: Diversity and complexity of signaling through peptidergic G protein-coupled receptors. 2004; Endocrinol 145:2645–52.

    Google Scholar 

  62. Freidinger RM. Nonpeptidic ligands for peptide and protein receptors. Curr Opin Chem Biol 1999; 3:395–406.

    Article  CAS  PubMed  Google Scholar 

  63. Gurrath M. Peptide-binding G protein-coupled receptors: new opportunities for drug design. Curr Med Chem 2001; 8:1605–48.

    CAS  PubMed  Google Scholar 

  64. Estriarte M, Rich D. Peptidomimetics for drug design. In: Abraham DJ, ed. Burger’s Medicinal Chemistry and Drug Discovery. Hoboken: Wiley-Interscience 2003:1(6):633–85.

    Google Scholar 

  65. Blakeney JS, Reid RC, Le GT et al. Nonpeptidic ligands for peptide-activated G protein-coupled receptors. Chem Rev 2007; 107:2960–3041.

    Article  CAS  PubMed  Google Scholar 

  66. Li C, Kim K. Neuropeptides ed. The C. elegans Research Community. WormBook, doi/10.1895/ wormbook.1.7.1, http://www.wormbook.org 2008.

    Google Scholar 

  67. Husson SJ, Mertens I, Janssen T et al. Neuropeptidergic signaling in the nematode Caenorhabditis elegans. Prog Neurobiol 2007; 82:33–55.

    Article  CAS  PubMed  Google Scholar 

  68. Isaac RE, Bland ND, Shirras AD. Neuropeptidases and the metabolic inactivation of insect neuropeptides. Gen Comp Endocrinol 2009; 162:8–17.

    Article  CAS  PubMed  Google Scholar 

  69. Han M, Park D, Vanderzalm PJ et al. Drosophila uses two distinct neuropeptide amidating enzymes, dPAL1 and dPAL2. J Neurochem 2004; 90:129–41.

    Article  CAS  PubMed  Google Scholar 

  70. Mair GR, Niciu MJ, Stewart MT et al. A functionally atypical amidating enzyme from the human parasite Schistosoma mansoni. FASEB J 2004; 18:114–21.

    Article  CAS  PubMed  Google Scholar 

  71. Peeters T, Matthijs G, Depoortere I et al. Erythromycin is a motilin receptor agonist. Am J Physiol 1989; 257:G470–4.

    CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Institute of Parasitology, McGill University, 21111 Lakeshore Road, Ste-Anne-de-Bellevue, QC, Canada, H9X 3V9

    Timothy G. Geary

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  1. Timothy G. Geary
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Editors and Affiliations

  1. Institute of Parasitology, McGill University, Montréal, Québec, Canada

    Timothy G. Geary PhD

  2. Parasitology, School of Biological Sciences, Medical Biology Centre, Queen’s University Belfast, Belfast, UK

    Aaron G. Maule PhD

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Geary, T.G. (2010). Nonpeptide Ligands for Peptidergic G Protein-Coupled Receptors. In: Geary, T.G., Maule, A.G. (eds) Neuropeptide Systems as Targets for Parasite and Pest Control. Advances in Experimental Medicine and Biology, vol 692. Springer, Boston, MA. https://doi.org/10.1007/978-1-4419-6902-6_2

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