The overall objective of this research is to gain better understanding of serotonin-activated adenylate cyclase and enzymes that are regulated by cyclic AMP in trematodes. We plan to use Fasciola hepatica to study the cyclase system in depth. We will solubilize, purify, and characterize the serotonin receptors and the GTP-regulatory protein component of the cyclase. We plan to characterize and isolate the substrate(s) of cyclic AMP-dependent protein kinase from Fasciola. This includes phosphofructokinase (PFK) which has just been purified in our laboratory. We will study the control of fluke PFK through phosphorylation, and the relationship between PFK structure and its function to meet the metabolic needs of the parasite. We will continue with our investigation on the nature of serotonin activated adenylate cyclase from Schistosoma mansoni. Some characterization studies will be done on the serotonin receptors to see how related they are to the Fasciola enzyme. We plan to identify serotonin analogs that act as agonists or antagonists on these receptors in adult schistosomes and in schistosomules, and examine their effect on development of the parasites. We will test the possiblity that serotonin antagonists can adversely affect adult schistosomes or schistosomules in vitro as well as in the host. One essential theme that runs through our research is identification of the differences as well as the similarities of properties of these enzymes and receptors in parasite and host. Our ultimate goal is to identify sites in the parasite that are amenable to pharmacological manipulation without affecting the host.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI016501-08
Application #
3126683
Study Section
Tropical Medicine and Parasitology Study Section (TMP)
Project Start
1980-04-01
Project End
1991-12-31
Budget Start
1988-01-01
Budget End
1988-12-31
Support Year
8
Fiscal Year
1988
Total Cost
Indirect Cost
Name
Stanford University
Department
Type
Schools of Medicine
DUNS #
800771545
City
Stanford
State
CA
Country
United States
Zip Code
94305
Mansour, J M; McCrossan, M V; Bickle, Q D et al. (2000) Schistosoma mansoni phosphofructokinase: immunolocalization in the tegument and immunogenicity. Parasitology 120 ( Pt 5):501-11
Su, J G; Mansour, J M; Mansour, T E (1996) Purification, kinetics and inhibition by antimonials of recombinant phosphofructokinase from Schistosoma mansoni. Mol Biochem Parasitol 81:171-8
Ding, J; Su, J G; Mansour, T E (1994) Cloning and characterization of a cDNA encoding phosphofructokinase from Schistosoma mansoni. Mol Biochem Parasitol 66:105-10
Iltzsch, M H; Bieber, D; Vijayasarathy, S et al. (1992) Cloning and characterization of a cDNA coding for the alpha-subunit of a stimulatory G protein from Schistosoma mansoni. J Biol Chem 267:14504-8
Webster, P J; Mansour, T E (1992) Conserved classes of homeodomains in Schistosoma mansoni, an early bilateral metazoan. Mech Dev 38:25-32
Webster, P J; Seta, K A; Chung, S C et al. (1992) A cDNA encoding an alpha-tubulin from Schistosoma mansoni. Mol Biochem Parasitol 51:169-70
Mahrenholz, A M; Hefta, S A; Mansour, T E (1991) Phosphofructokinase from Fasciola hepatica: sequence of the cAMP-dependent protein kinase phosphorylation site. Arch Biochem Biophys 288:463-7
Conner, D A; Mansour, T E (1990) Serotonin receptor-mediated activation of adenylate cyclase in the neuroblastoma NCB.20: a novel 5-hydroxytryptamine receptor. Mol Pharmacol 37:742-51
Zurita, M; Bieber, D; Mansour, T E (1989) Identification, expression and in situ hybridization of an eggshell protein gene from Fasciola hepatica. Mol Biochem Parasitol 37:11-7
Mansour, J M; Mansour, T E (1989) Identification of GTP-binding proteins in Fasciola hepatica and Schistosoma mansoni by immunoblotting. Mol Biochem Parasitol 36:11-8

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