Skip to main content

Hypotensive Proteins from Hematophagous Animals

  • Chapter
  • First Online:
Book cover Toxins and Hemostasis

Abstract

Diverse arthropods exploit vertebrate blood as a food resource, despite the fact that this resource is defended by an array of haemostatic, inflammatory, and immune responses, as well as overt defensive behaviors. These defenses have selected for a broad array of antihaemostatic, anti-inflammatory, and immunomodulatory factors, which are secreted in the saliva of the blood-feeder and injected into the wound during the feeding process. Haemostasis includes three interacting branches: platelet activation and aggregation, vasoconstriction, and coagulation (or clotting). This review deals with salivary factors that counter the vasoconstriction that normally results following vascular injury, but as the branches of haemostasis overlap, and indeed haemostasis interacts with inflammation and immunity, some molecules with vasodilatory (hypotensive) activity may also affect other aspects of the vertebrate response, in which case they are also discussed. Blood-feeding has evolved on numerous independent occasions, leading to a wide diversity of molecules with hypotensive activity amongst extant arthropods. These molecules exploit mechanisms that include direct interaction with vertebrate receptors or signaling pathways leading to vasodilation, sequestration of endogenously generated vasoconstrictors, and enzymatic destruction of vasoconstrictors. Some vasodilators, specifically the nitrophorins from Rhodnius and Cimex, allow the arthropod to store physiological amounts of nitric oxide and secrete it into the bite site during the course of the blood meal. Finally, several instances are noted where arthropod saliva is known to contain hypotensive activity, but the molecules involved have not been identified.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Andersen, J.F., 2009. Structure and mechanism in salivary proteins from blood-feeding arthropods. Toxicon [Epub ahead of print]. doi: 10.1016/j.toxicon.2009.11.002

    Google Scholar 

  • Andersen, J.F., Champagne, D.E., Weichsel, A., Ribeiro, J.M., Balfour, C.A., Dress, V., Montfort, W.R., 1997. Nitric oxide binding and crystallization of recombinant nitrophorin I, a nitric oxide transport protein from the blood-sucking bug Rhodnius prolixus . Biochemistry 36, 4423–4428.

    Article  PubMed  CAS  Google Scholar 

  • Andersen, J.F., Ding, X.D., Balfour, C., Shokhireva, T.K., Champagne, D.E., Walker, F.A., Montfort, W.R., 2000. Kinetics and equilibria in ligand binding by nitrophorins 1–4: evidence for stabilization of a nitric oxide-ferriheme complex through a ligand induced conformational trap. Biochemistry 39, 10118–10131.

    Article  PubMed  CAS  Google Scholar 

  • Andersen, J.F., Francischetti, I.M., Valenzuela, J.G., Schuck, P., Ribeiro, J.M., 2003. Inhibition of hemostasis by a high affinity biogenic amine-binding protein from the saliva of a blood-feeding insect. J. Biol. Chem. 278, 4611–4617.

    Article  PubMed  CAS  Google Scholar 

  • Andersen, J.F., Gudderra, N.P., Francischetti, I.M., Valenzuela, J.G., Ribeiro, J.M., 2004. Recognition of anionic phospholipid membranes by an antihemostatic protein from a blood-feeding insect. Biochemistry 43, 6987–6994.

    Article  PubMed  CAS  Google Scholar 

  • Andersen, J.F., Montfort, W.R., 2000. The crystal structure of nitrophorin 2. A trifunctional antihemostatic protein from the saliva of Rhodnius prolixus . J. Biol. Chem. 275, 30496–30503.

    Article  PubMed  CAS  Google Scholar 

  • Anderson, J.M., Oliveira, F., Kamhawi, S., Mans, B.J., Reynoso, D., Seitz, A.E., Lawyer, P., Garfield, M., Pham, M., Valenzuela, J.G., 2006. Comparative salivary gland transcriptomics of sandfly vectors of visceral leishmaniasis. BMC Genomics 7, 52.

    Article  PubMed  CAS  Google Scholar 

  • Andersen, J.F., Pham, V.M., Meng, Z., Champagne, D.E., Ribeiro, J.M., 2009. Insight into the sialome of the Black Fly, Simulium vittatum. J. Proteome Res. 8, 1474–1488.

    Article  PubMed  CAS  Google Scholar 

  • Andersen, J.F., Weichsel, A., Balfour, C.A., Champagne, D.E., Montfort, W.R., 1998. The crystal structure of nitrophorin 4 at 1.5 A resolution: transport of nitric oxide by a lipocalin-based heme protein. Structure 6, 1315–1327.

    Article  PubMed  CAS  Google Scholar 

  • Araujo, R.N., Soares, A.C., Paim, R.M., Gontijo, N.F., Gontijo, A.F., Lehane, M.J., Pereira, M.H., 2009. The role of salivary nitrophorins in the ingestion of blood by the triatomine bug Rhodnius prolixus (Reduviidae: Triatominae). Insect Biochem. Mol. Biol .39, 83–89.

    Article  PubMed  CAS  Google Scholar 

  • Arcá, B., Lombardo, F., de Lara Capurro, M., della Torre, A., Dimopoulos, G., James, A.A., Coluzzi, M., 1999. Trapping cDNAs encoding secreted proteins from the salivary glands of the malaria vector Anopheles gambiae. Proc. Natl. Acad. Sci. U.S.A. 96, 1516–1521.

    Article  PubMed  Google Scholar 

  • Arcà, B., Lombardo, F., Lanfrancotti, A., Spanos, L., Veneri, M., Louis, C., Coluzzi, M., 2002. A cluster of four D7-related genes is expressed in the salivary glands of the African malaria vector Anopheles gambiae. Insect Mol. Biol. 11, 47–55.

    Article  PubMed  Google Scholar 

  • Assumpção, T.C., Francischetti, I.M., Andersen, J.F., Schwarz, A., Santana, J.M., Ribeiro, J.M., 2008. An insight into the sialome of the blood-sucking bug Triatoma infestans, a vector of Chagas’ disease. Insect Biochem. Mol. Biol. 38, 213–232.

    Article  PubMed  CAS  Google Scholar 

  • Beerntsen, B.T., Champagne, D.E., Coleman, J.L., Campos, Y.A., James, A.A., 1999. Characterization of the Sialokinin I gene encoding the salivary vasodilator of the yellow fever mosquito, Aedes aegypti. Insect Mol. Biol. 8, 459–467.

    Article  PubMed  CAS  Google Scholar 

  • Bergman, D.K., 1996. Mouthparts and feeding mechanisms of haematophagous arthropods, in: Wikel, S.K. (Ed.), The Immunology of Host-Ectoparasitic Arthropod Relationships. CAB International, Wallingford, pp. 30–61.

    Google Scholar 

  • Bowman, A.S., Dillwith, J.W., Sauer, J.R., 1996. Tick salivary prostaglandins: presence, origin, and significance. Parasitol. Today 12, 388–395.

    Article  PubMed  CAS  Google Scholar 

  • Bowman, A.S., Gengler, C.L., Surdick, M.R., Zhu, K., Essenberg, R.C., Sauer, J.R., Dillwith, J.W., 1997. A novel phospholipase A2 activity in saliva of the lone star tick, Amblyomma americanum (L.). Exp. Parasitol. 87, 121–132.

    Article  PubMed  CAS  Google Scholar 

  • Bowman, A.S., Sauer, J.R., Neese, P.A., Dillwith, J.W., 1995. Origin of arachidonic acid in the salivary glands of the lone star tick, Amblyomma americanum. Insect Biochem. Mol. Biol. 25, 225–233.

    Article  PubMed  CAS  Google Scholar 

  • Brossard, M., Wikel, S.K., 2004. Tick immunobiology. Parasitology 129(Suppl), S161–S176.

    Article  PubMed  CAS  Google Scholar 

  • Calvo, E., Dao, A., Pham, V.M., Ribeiro, J.M., 2007. An insight into the sialome of Anopheles funestus reveals an emerging pattern in anopheline salivary protein families. Insect Biochem. Mol. Biol. 37, 164–175.

    Article  PubMed  CAS  Google Scholar 

  • Calvo, E., deBianchi, A.G., James, A.A., Marinotti, O., 2002. The major acid soluble proteins of adult female Anopheles darlingi salivary glands include a member of the D7-related family of proteins. Insect Biochem. Mol. Biol. 32, 1419–1427.

    Article  PubMed  CAS  Google Scholar 

  • Calvo, E., Mans, B.J., Andersen, J.F., Ribeiro, J.M., 2006. Function and evolution of a mosquito salivary protein family. J. Biol. Chem. 281, 1935–1942.

    Article  PubMed  CAS  Google Scholar 

  • Calvo, E., Mans, B.J., Ribeiro, J.M., Andersen, J.F., 2009. Multifunctionality and mechanism of ligand binding in a mosquito anti-inflammatory protein. Proc. Natl. Acad. Sci. U.S.A. 106, 3728–3733.

    Article  PubMed  CAS  Google Scholar 

  • Campbell, C.L., Vandyke, K.A., Letchworth, G.J., Drolet, B.S., Hanekamp, T., Wilson, W.C., 2005. Midgut and salivary gland transcriptomes of the arbovirus vector Culicoides sonorensis (Diptera: Ceratopogonidae). Insect Mol. Biol. 14, 121–136.

    Article  PubMed  CAS  Google Scholar 

  • Champagne, D., 2005. Antihemostatic molecules from saliva of blood-feeding arthropods. Pathophysiol. Haemost. Thromb. 34, 221–227

    Article  PubMed  CAS  Google Scholar 

  • Champagne, D.E., Ribeiro, J.M., 1994. Sialokinin I and II: vasodilatory tachykinins from the yellow fevermosquito Aedes aegypti. Proc. Natl. Acad. Sci. U.S.A. 91, 138–142.

    Article  PubMed  CAS  Google Scholar 

  • Champagne, D.E., Nussenzveig, R.H., Ribeiro, J.M., 1995. Purification, partial characterization, and cloning of nitric oxide-carrying heme proteins (nitrophorins) from salivary glands of the blood-sucking insect Rhodnius prolixus. J. Biol. Chem. 270, 8691–8695.

    Article  PubMed  CAS  Google Scholar 

  • Cupp, M.S., Ribeiro, J.M., Champagne, D.E., Cupp, E.W., 1998. Analyses of cDNA and recombinant protein for a potent vasoactive protein in saliva of a blood-feeding black fly, Simulium vittatum. J. Exp. Biol. 201, 1553–1561.

    PubMed  CAS  Google Scholar 

  • Cupp, M.S., Ribeiro, J.M.C., Cupp, E.W., 1994. Vasodilative activity in black fly salivary glands. Am. J. Trop. Med. Hyg. 50, 241–246.

    PubMed  CAS  Google Scholar 

  • Dickinson, R.G., O’Hagan, J.E., Shotz, M., Binnington, K.C., Hegarty, M.P., 1976. Prostaglandin in the saliva of the cattle tick Boophilus microplus. Aust. J. Exp. Biol. Med. Sci. 54, 475–486.

    Article  PubMed  CAS  Google Scholar 

  • Doolittle, R.F., 2009. Step-by-step evolution of vertebrate blood coagulation. Cold Spring Harbor Symp. Quant. Biol. [Epub ahead of print]. doi: 10.1101/sqb.2009.74.001

    Google Scholar 

  • Doolittle, R.F., Feng, D.F., 1987. Reconstructing the evolution of vertebrate blood coagulation from a consideration of the amino acid sequences of clotting proteins. Cold Spring Harbor Symp. Quant. Biol. LII, 869–874.

    Article  Google Scholar 

  • Francischetti, I.M., Ribeiro, J.M., Champagne, D., Andersen, J., 2000. Purification, cloning, expression, and mechanism of action of a novel platelet aggregation inhibitor from the salivary gland of the bloodsucking bug, Rhodnius prolixus. J. Biol. Chem. 275, 12639–12650.

    Article  PubMed  CAS  Google Scholar 

  • Francischetti, I.M., Sa-Nunes, A., Mans, B.J., Santos, I.M., Ribeiro, J.M., 2009. The role of saliva in tick feeding. Front. Biosci. 14, 2051–2088.

    Article  PubMed  CAS  Google Scholar 

  • Francischetti, I.M., Valenzuela, J.G., Pham, V.M., Garfield, M.K., Ribeiro ,J.M., 2002. Toward a catalog for the transcripts and proteins (sialome) from the salivary gland of the malaria vector Anopheles gambiae. J. Exp. Biol. 205, 2429–2451.

    PubMed  CAS  Google Scholar 

  • Fry, B.G., Roelants, K., Champagne, D.E., Scheib, H., Tyndall, J.D., King, G.F., Nevalainen, T.J., Norman, J.A., Lewis, R.J., Norton, R.S., Renjifo, C., de la Vega, R.C., 2009. The toxicogenomic multiverse: convergent recruitment of proteins into animal venoms. Annu. Rev. Genomics Hum. Genet. 10, 483–511.

    Article  PubMed  CAS  Google Scholar 

  • Gillett, J.D., 1967. Natural selection and feeding speed in a blood-sucking insect. Proc. Roy. Soc. Lond. B. Biol. Sci. 167, 316–329.

    Article  CAS  Google Scholar 

  • Golodne, D.M., Monteiro, R.Q., Graca-Souza, A.V., Silva-Neto, M.A., Atella, G.C., 2003. Lysophosphatidylcholine acts as an anti-hemostatic molecule in the saliva of the blood-sucking bug Rhodnius prolixus. J. Biol. Chem. 278, 27766–27771.

    Article  PubMed  CAS  Google Scholar 

  • Grevelink, S.A., Osborne, Loscalzo, J. Lerner, E.A., 1995. Vasorelaxant and second messenger effects of maxadilan. J. Pharmacol. Exp. Ther. 272, 33–37.

    PubMed  CAS  Google Scholar 

  • Grevelink, S.A., Youssef, D.E., Loscalzo, J., Lerner, E.A., 1993. Salivary-gland extracts from the deerfly contain a potent inhibitor of platelet aggregation. Proc. Natl. Acad. Sci. U.S.A. 90, 9155–9158.

    Article  PubMed  CAS  Google Scholar 

  • Grimaldi, D., Engel, M. 2005. Evolution of the insects. Cambridge University Press, New York.

    Google Scholar 

  • Gudderra, N.P., Ribeiro, J.M., Andersen, J.F., 2005. Structural determinants of factor IX(a) binding in nitrophorin 2, a lipocalin inhibitor of the intrinsic coagulation pathway. J. Biol. Chem. 280, 25022–25028.

    Article  PubMed  CAS  Google Scholar 

  • Higgs, G.A., Vane, J.R., Hart, R.J., Porter, C., Wilson, R.G., 1976. Prostaglandins in the saliva of the cattle tick, Boophilus microplus (Canestrini) (Acarina: Ixodidae). Bull. Entomol. Res. 66, 665–670.

    Article  CAS  Google Scholar 

  • Hollander, A.L., Wright, R.E., 1980. Impact of tabanids on cattle: blood meal size and preferred feeding sites. J. Econ. Entomol. 73, 431–433

    PubMed  CAS  Google Scholar 

  • Isawa, H., Yuda, M., Yoneda, K., Chinzei, Y., 2000. The insect salivary protein, prolixin-S, inhibits factor IXa generation and Xase complex formation in the blood coagulation pathway. J. Biol. Chem. 275, 6636–6641.

    Article  PubMed  CAS  Google Scholar 

  • James, A.A., Blackmer, K., Marinotti, O., Ghosn, C.R., Racioppi, J.V., 1991. Isolation and characterization of the gene expressing the major salivary gland protein of the female mosquito, Aedes aegypti. Mol. Biochem. Parasitol. 44, 245–253.

    Article  PubMed  CAS  Google Scholar 

  • Jones, D., 1998. The neglected saliva: medically important toxins in the saliva of human lice. Parasitology 116(Suppl), S73–S81.

    Article  PubMed  Google Scholar 

  • Kazimírová, M., Šulanová, M., Kozánek, M., Takác, P., Labuda, M., Nuttall, P.A., 2001. Identification of anticoagulant activities in salivary gland extracts of four horsefly species (Diptera: Tabanidae). Haemostasis 31, 294–305.

    PubMed  Google Scholar 

  • Kemp, D.H., Hales, J.R., Schleger, A.V. Fawcett, A.A., 1983. Comparison of cutaneous hyperemia in cattle elicited by larvae of Boophilus microplus and by prostaglandins and other mediators. Experientia 39, 725–727.

    Article  PubMed  CAS  Google Scholar 

  • Koh, C.Y., Kini, R.M. 2009. Molecular diversity of anticoagulants from haematophagous animals. Thromb. Haemost. 102, 437–453.

    PubMed  CAS  Google Scholar 

  • Lanzaro, G.C., Lopes, A.H., Ribeiro, J.M., Shoemaker, C.B., Warburg, A., Soares, M., Titus, R.G., 1999. Variation in the salivary peptide, maxadilan, from species in the Lutzomyia longipalpis complex. Insect Mol. Biol. 8, 267–275.

    Article  PubMed  CAS  Google Scholar 

  • Law, J.H., Ribeiro, J.M., Wells, M.A., 1992. Biochemical insights derived from insect diversity. Annu. Rev. Biochem. 61, 87–111.

    Article  PubMed  CAS  Google Scholar 

  • Lerner, E.A., Ribeiro, J.M., Nelson, R.J., Lerner, M.R., 1991. Isolation of maxadilan, a potent vasodilatory peptide from the salivary glands of the sand fly Lutzomyia longipalpis . J. Biol. Chem. 266, 11234–11236.

    PubMed  CAS  Google Scholar 

  • Lerner, E.A., Shoemaker, C.B., 1992. Maxadilan: cloning and functional expression of the gene encoding this potent vasodilator peptide. J. Biol. Chem. 267, 1062–1066.

    PubMed  CAS  Google Scholar 

  • Lu, S.M,. Lu, W., Qasim, M.A., Anderson, S., Apostol, I., Ardelt, W., Bigler, T., Chiang, Y.W., Cook, J., James, M.N., Kato, I., Kelly, C., Kohr, W., Komiyama, T., Lin, T.Y., Ogawa, M., Otlewski, J., Park, S.J., Qasim, S., Ranjbar, M., Tashiro, M., Warne, N., Whatley, H., Wieczorek, A., Wieczorek, M., Wilusz, T., Wynn, R., Zhang, W., Laskowski, M., Jr., 2001. Predicting the reactivity of proteins from their sequence alone: Kazal family of protein inhibitors of serine proteinases. Proc. Natl. Acad. Sci. U.S.A. 98, 1410–1415.

    Article  PubMed  CAS  Google Scholar 

  • Ma, D., Wang, Y., Yang, H., Wu, J., An, S., Gao, L., Xu, X., Lai, R., 2009. Anti-thrombosisrepertoire of blood-feeding horsefly salivary glands. Mol. Cell Proteomics 8, 2071–2079.

    Article  PubMed  CAS  Google Scholar 

  • Maes, E.M., Weichsel, A., Andersen, J.F., Shepley, D., Montfort, W.R., 2004. Role of binding site loops in controlling nitric oxide release: structure and kinetics of mutant forms of nitrophorin 4. Biochemistry 43, 6679–6690.

    Article  PubMed  CAS  Google Scholar 

  • Mans, B.J., Calvo, E., Ribeiro, J.M., Andersen, J.F., 2007. The crystal structure of D7r4, a salivary biogenic amine-binding protein from the malaria mosquito Anopheles gambiae. J. Biol. Chem. 282, 36626–36633.

    Article  PubMed  CAS  Google Scholar 

  • Mans, B.J., Ribeiro, J.M., 2008a. Function, mechanism and evolution of the moubatin-clade of soft tick lipocalins. Insect Biochem. Mol. Biol. 38, 841–852.

    Article  PubMed  CAS  Google Scholar 

  • Mans, B.J., Ribeiro, J.M., 2008b. A novel clade of cysteinyl leukotriene scavengers in soft ticks. Insect Biochem. Mol. Biol. 38, 862–870.

    Article  PubMed  CAS  Google Scholar 

  • Mans, B.J., Ribeiro, J.M., Andersen, J.F., 2008. Structure, function, and evolution of biogenic amine-binding proteins in soft ticks. J. Biol. Chem. 283, 18721–18733.

    Article  PubMed  CAS  Google Scholar 

  • Mesquita, R.D., Carneiro, A.B., Bafica, A., Gazos-Lopes, F., Takiya, C.M., Souto-Padron, T., Vieira, D.P., Ferreira-Pereira, A., Almeida, I.C., Figueiredo, R.T., Porto, B.N., Bozza, M.T., Graça-Souza, AV., Lopes, A.H., Atella, G.C., Silva-Neto, M.A., 2008. Trypanosoma cruzi infection is enhanced by vector saliva through immunosuppressant mechanisms mediated by lysophosphatidylcholine. Infect. Immun. 76, 5543–5552.

    Article  PubMed  CAS  Google Scholar 

  • Milleron, R.S., Mutebi, J.P., Valle, S., Montoya, A., Yin, H., Soong, L., Lanzaro, G.C., 2004. Antigenic diversity in maxadilan, a salivary protein from the sand fly vector of American visceral leishmaniasis. Am. J. Trop. Med. Hyg. 70, 286–293.

    PubMed  CAS  Google Scholar 

  • Moreira, M.F., Coelho, H.S., Zingali, R.B., Oliveira, P.L., Masuda, H., 2003. Changes in salivary nitrophorin profile during the life cycle of the blood-sucking bug Rhodnius prolixus. Insect Biochem. Mol. Biol. 33, 23–28.

    Article  PubMed  CAS  Google Scholar 

  • Moro, O., Lerner, E.A., 1997. Maxadilan, the vasodilator from sand flies, is a specific pituitary adenylate cyclase activating peptide type I receptor agonist. J. Biol. Chem. 272, 966–970.

    Article  PubMed  CAS  Google Scholar 

  • Nussenzveig, R.H., Bentley, D.L., Ribeiro, J.M., 1995. Nitric oxide loading of the salivary nitric-oxide-carrying hemoproteins (nitrophorins) in the blood-sucking bug Rhodnius prolixus. J. Exp. Biol. 198, 1093–1098.

    PubMed  CAS  Google Scholar 

  • Oldham, N.J., Lissina, O., Nunn, M.A., Paesen, G.C., 2003. Non-denaturing electrospray ionisation-mass spectrometry reveals ligand selectivity in histamine-binding protein RaHBP2. Org. Biomol. Chem. 1, 3645–3646.

    Article  PubMed  CAS  Google Scholar 

  • Paesen, G.C., Adams, P.L., Harlos, K., Nuttall, P.A., Stuart, D.I., 1999. Tick histamine-binding proteins: isolation, cloning, and three-dimensional structure. Mol. Cell 3, 661–671.

    Article  PubMed  CAS  Google Scholar 

  • Paesen, G.C., Adams, P.L., Nuttall, P.A., Stuart, D.L., 2000. Tick histamine-binding proteins: lipocalins with a second binding cavity. Biochim. Biophys. Acta 1482, 92–101.

    Article  PubMed  CAS  Google Scholar 

  • Paesen, G.C., Siebold, C., Dallas, M.L., Peers, C., Harlos, K., Nuttall, P.A., Nunn, M.A., Stuart, D.I., Esnouf, R.M., 2009. An ion-channel modulator from the saliva of the brown ear tick has a highly modified Kunitz/BPTI structure. J. Mol. Biol. 389, 734–747.

    Article  PubMed  CAS  Google Scholar 

  • Perez de Leon, A.A., Ribeiro, J.M., Tabachnick, W.J., Valenzuela, J.G., 1997. Identification of a salivary vasodilator in the primary North American vector of bluetongue viruses, Culicoides variipennis. Am. J. Trop. Med. Hyg. 57, 375–381.

    Google Scholar 

  • Rai, K.S., Black, W.C., 4th., 1999. Mosquito genomes: structure, organization, and evolution. Adv. Genet. 41, 1–33.

    Article  PubMed  CAS  Google Scholar 

  • Rajská, P., Knezl, V., Kazimírová, M., Takáč, P., Roller, L., Vidlička, L., Čiampor, F., Labuda, M., Weston-Davies, W., Nuttall, P.A. 2007. Effects of horsefly (Tabanidae) salivary gland extracts on isolated perfused rat heart. Med. Vet. Entomol. 21, 384–389.

    Article  PubMed  Google Scholar 

  • Rajská, P., Pechánová, O., Takác, P., Kazimírová, M., Roller, L., Vidlicka, L., Ciampor, F., Labuda, M., Nuttall, P.A., 2003. Vasodilatory activity in horsefly and deerfly salivary glands. Med. Vet. Entomol. 17, 395–402.

    Article  PubMed  Google Scholar 

  • Reddy, V.B., Kounga, K., Mariano, F., Lerner, E.A., 2000. Chrysoptin is a potent glycoprotein IIb/IIIa fibrinogen receptor antagonist present in salivary gland extracts of the deerfly. J. Biol. Chem. 275, 15861–15867.

    Article  PubMed  CAS  Google Scholar 

  • Ribeiro, J.M.C., 1987. Role of saliva in blood-feeding by arthropods. Annu. Rev. Entomol. 32, 463–478.

    Article  PubMed  CAS  Google Scholar 

  • Ribeiro, J.M., 1992. Characterization of a vasodilator from the salivary glands of the yellow fever mosquito Aedes aegypti. J. Exp. Biol. 165, 61–71.

    PubMed  CAS  Google Scholar 

  • Ribeiro, J.M.C. 1995. Blood-feeding arthropods: live syringes or invertebrate pharmacologists? Infect Agents Dis. 4, 143–152.

    PubMed  CAS  Google Scholar 

  • Ribeiro, J.M., 1996. NAD(P)H-dependent production of oxygen reactive species by the salivary glands of the mosquito Anopheles albimanus. Insect Biochem. Mol. Biol. 26, 715–720.

    Article  PubMed  CAS  Google Scholar 

  • Ribeiro, J.M., 2000. Blood-feeding in mosquitoes: probing time and salivary gland anti-haemostatic activities in representatives of three genera (Aedes, Anopheles, Culex). Med. Vet. Entomol. 14, 142–148.

    Article  PubMed  CAS  Google Scholar 

  • Ribeiro, J.M., Charlab, R., Pham, V.M., Garfield, M., Valenzuela, J.G., 2004. An insight into the salivary transcriptome and proteome of the adult female mosquito Culex pipiens quinquefasciatus. Insect Biochem. Mol. Biol. 34, 543–563.

    Article  PubMed  CAS  Google Scholar 

  • Ribeiro, J.M., Evans, P.M., MacSwain, J.L., Sauer, J.. 1992. Amblyomma americanum: characterization of salivary prostaglandins E2 and F2 α by RP-HPLC/bioassay and gas chromatography-mass spectrometry. Exp. Parasitol. 74, 112–116.

    Article  PubMed  CAS  Google Scholar 

  • Ribeiro, J.M.C., Francischetti, I.M.B., 2003. Role of arthropod saliva in blood feeding: sialome and post-sialome perspectives. Annu. Rev. Entomol. 48, 73–88.

    Article  PubMed  CAS  Google Scholar 

  • Ribeiro, J.M., Hazzard, J.M., Nussenzveig, R.H., Champagne, D.E., Walker, F.A., 1993. Reversible binding of nitric oxide by a salivary heme protein from a bloodsucking insect. Science 260, 539–541.

    Article  PubMed  CAS  Google Scholar 

  • Ribeiro, J.M., Katz, O., Pannell, L.K., Waitumbi, J., Warburg, A., 1999. Salivary glands of the sand fly Phlebotomus papatasi contain pharmacological amounts of adenosine and 5-AMP. J. Exp. Biol. 202, 1551–1559.

    PubMed  CAS  Google Scholar 

  • Ribeiro, J.M., Marinotti, O., Gonzales, R., 1990. A salivary vasodilator in the blood-sucking bug, Rhodnius prolixus. Br. J. Pharmacol. 101, 932–936.

    Article  PubMed  CAS  Google Scholar 

  • Ribeiro, J.M., Nussenzveig, R.H., 1993. Nitric oxide synthase activity from a hematophagous insect salivary gland. FEBS Lett. 330, 165–168.

    Article  PubMed  CAS  Google Scholar 

  • Ribeiro, J.M., Schneider, M., Guimarães, J.A., 1995. Purification and characterization of prolixin S (nitrophorin 2), the salivary anticoagulant of the blood-sucking bug Rhodnius prolixus. Biochem. J. 308, 243–249.

    PubMed  CAS  Google Scholar 

  • Ribeiro, J.M., Schneider, M., Isaias, T., Jurberg, J., Galvao, C., Guimaraes, J.A., 1998. Role of salivary antihemostatic components in blood feeding by triatomine bugs (Heteroptera). J. Med. Entomol. 35, 599–610.

    PubMed  CAS  Google Scholar 

  • Ribeiro, J.M., Valenzuela, J.G., 1999. Purification and cloning of the salivary peroxidase/catechol oxidase of the mosquito Anopheles albimanus. J. Exp. Biol. 202, 809–816.

    PubMed  CAS  Google Scholar 

  • Ribeiro, J.M., Walker, F.A., 1994. High affinity histamine- binding and antihistaminic activity of the salivary nitric oxide-carrying heme protein (nitrophorin) of Rhodnius prolixus. J. Exp. Med. 180, 2251–2257.

    Article  PubMed  CAS  Google Scholar 

  • Sangamnatdej, S., Paesen, G.C., Slovak, M., Nuttall, P.A., 2002. A high affinity serotonin- and histamine-binding lipocalin from tick saliva. Insect Mol. Biol. 11, 79–86.

    Article  PubMed  CAS  Google Scholar 

  • Santos, A., Ribeiro, J.M., Lehane, M.J., Gontijo, N.F., Viols, A.B., Sant’Anna, M.R., Nascimento, Araujo, R., Grisard, E.C., Pereira, M.H., 2007. The sialotranscriptome of the blood-sucking bug Triatoma brasiliensis (Hemiptera: Triatominae). Insect Biochem. Mol. Biol. 37, 702–712.

    Article  PubMed  CAS  Google Scholar 

  • Sarkis, J.J., Guimarães, J.A., Ribeiro, J.M., 1986. Salivary apyrase of Rhodnius prolixus: kinetics and purification. Biochem. J. 233, 885–891.

    PubMed  CAS  Google Scholar 

  • Schneider, B.S., Higgs, S., 2008. The enhancement of arbovirus transmission and disease by mosquito saliva is associated with modulation of the host immune response. Trans. R. Soc. Trop. Med. Hyg. 102, 400–408.

    Article  PubMed  Google Scholar 

  • Sun, J., Yamaguchi, M., Yuda, M., Miura, K., Takeya, H., Hirai, M., Matsuoka, H., Ando, K., Watanabe, T., Suzuki, K., Chinzei, Y., 1996. Purification, characterization and cDNA cloning of a novel anticoagulant of the intrinsic pathway, (prolixin-S) from salivary glands of the blood sucking bug, Rhodnius prolixus. Thromb. Haemost. 75, 573–577.

    PubMed  CAS  Google Scholar 

  • Sun, J., Yuda, M., Miura, K., Chinzei, Y., 1998. Characterization and cDNA cloning of a hemoprotein in the salivary glands of the blood-sucking insect, Rhodnius prolixus. Insect Biochem. Mol. Biol. 28, 191–200.

    Article  PubMed  CAS  Google Scholar 

  • Takac, P., Nunn, M.A., Meszaros, J., Pechanova, O., Vrbjar, N., Vlasakova, P., Kozanek, M., Kazimirova, M., Hart, G., Nuttall, P.A., Labuda, M., 2006. Vasotab, a vasoactive peptide from horse fly Hybomitra bimaculata (Diptera: Tabanidae) salivary glands. J. Exp. Biol. 209, 343–352

    Article  PubMed  CAS  Google Scholar 

  • Titus, R.G., Bishop, J.V., Mejia, J.S., 2006. The immunomodulatory factors of arthropod saliva and the potential for these factors to serve as vaccine targets to prevent pathogen transmission. Parasite Immunol. 28, 131–141.

    PubMed  CAS  Google Scholar 

  • Valenzuela, J.G., 2002. High-throughput approaches to study salivary proteins and genes from vectors of disease. Insect Biochem. Mol. Biol. 32, 1199–1209.

    Article  PubMed  CAS  Google Scholar 

  • Valenzuela, J.G., Charlab, R., Gonzalez, E.C., de Miranda-Santos, I.K., Marinotti, O., Francischetti, I.M., Ribeiro, J.M., 2002. The D7 family of salivary proteins in blood sucking diptera. Insect Mol. Biol. 11, 149–155.

    Article  PubMed  CAS  Google Scholar 

  • Valenzuela, J.G., Francischetti, I.M., Pham, V.M., Garfield, M.K., Ribeiro, J.M., 2003. Exploring the salivary gland transcriptome and proteome of the Anopheles stephensi mosquito. Insect Biochem. Mol. Biol. 33, 717–732.

    Article  PubMed  CAS  Google Scholar 

  • Valenzuela, J.G., Ribeiro, J.M., 1998. Purification and cloning of the salivary nitrophorin from the hemipteran Cimex lectularius. J. Exp. Biol. 201, 2659–2664.

    PubMed  CAS  Google Scholar 

  • Valenzuela, J.G., Walker, F.A., Ribeiro, J.M., 1995. A salivary nitrophorin (nitric-oxide-carrying hemoprotein) in the bedbug Cimex lectularius. J. Exp. Biol. 198, 1519–1526.

    PubMed  CAS  Google Scholar 

  • Weichsel, A., Andersen, J.F., Champagne, D.E., Walker, F.A., Montfort, W.R., 1998. Crystal structures of a nitric oxide transport protein from a blood-sucking insect. Nat. Struct. Biol. 5, 304–309.

    Article  PubMed  CAS  Google Scholar 

  • Weichsel, A., Andersen, J.F., Roberts, S.A., Montfort, W.R., 2000. Nitric oxide binding to nitrophorin 4 induces complete distal pocket burial. Nat. Struct. Biol. 7, 551–554.

    Article  PubMed  CAS  Google Scholar 

  • Weichsel, A., Maes, E.M., Andersen, J.F., Valenzuela, J.G., Shokhireva, T., Walker, F.A., Montfort, W.R., 2005. Heme-assisted S-nitrosation of a proximal thiolate in a nitric oxide transport protein. Proc. Natl. Acad. Sci. U.S.A. 102, 594–599.

    Article  PubMed  CAS  Google Scholar 

  • Wynn, R., Zhang, W., Laskowski, M., Jr., 2001. Predicting the reactivity of proteins from their sequence alone: Kazal family of protein inhibitors of serine proteinases. Proc. Natl. Acad. Sci. U.S.A. 98, 1410–1415.

    Article  PubMed  Google Scholar 

  • Yuda, M., Higuchi, K., Sun, J., Kureishi, Y., Ito, M., Chinzei, Y., 1997. Expression, reconstitution and characterization of prolixin-S as a vasodilator – a salivary gland nitric-oxide-binding hemoprotein of Rhodnius prolixus. Eur. J. Biochem. 249, 337–342.

    Article  PubMed  CAS  Google Scholar 

  • Yuda, M., Hirai, M., Miura, K., Matsumura, H., Ando, K., Chinzei, Y., 1996. cDNA cloning, expression and characterization of nitric-oxide synthase from the salivary glands of the blood-sucking insect Rhodnius prolixus. Eur. J. Biochem. 242, 807–812.

    Article  PubMed  CAS  Google Scholar 

  • Xu, X., Yang, H., Ma, D., Wu, J., Wang, Y., Song, Y., Wang, X., Lu, Y., Yang, J., Lai, R.. 2008. Toward an understanding of the molecular mechanism for successful blood feeding by coupling proteomics analysis with pharmacological testing of horsefly salivary glands. Mol. Cell. Proteomics 7, 582–590.

    PubMed  CAS  Google Scholar 

  • Zhu, K., Bowman, A.S., Dillwith, J.W., Sauer, J.R., 1998. Phospholipase A2 activity in salivary glands and saliva of the lone star tick (Acari: Ixodidae) during tick feeding. J. Med. Entomol. 35, 500–504.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to P. Takáč .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2010 Springer Science+Business Media B.V.

About this chapter

Cite this chapter

Takáč, P., Tsujimoto, H., Champagne, D. (2010). Hypotensive Proteins from Hematophagous Animals. In: Kini, R., Clemetson, K., Markland, F., McLane, M., Morita, T. (eds) Toxins and Hemostasis. Springer, Dordrecht. https://doi.org/10.1007/978-90-481-9295-3_38

Download citation

Publish with us

Policies and ethics