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Gene Review

Spr  -  sepiapterin reductase (7,8...

Rattus norvegicus

Synonyms: SPR, Sepiapterin reductase
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Disease relevance of Spr


High impact information on Spr

  • Within the dendrites the SPR undergoes a striking translocation from the plasma membrane to endosomes, and these dendrites also undergo a morphological reorganization, changing from a structure of rather uniform diameter to one characterized by large, swollen varicosities connected by thin fibers [6].
  • We have investigated this phenomenon in rat striatum, using substance P (SP)-induced internalization of the SP receptor (SPR) as our model system [6].
  • These data demonstrate that in the central nervous system in vivo, SP induces a rapid and widespread SPR internalization in the cell bodies and dendrites and a structural reorganization of the dendrites [6].
  • Electron microscopic analysis in cortex, striatum, and spinal cord revealed that approximately 70% of the surface membrane of immunoreactive neurons is SPR laden [7].
  • Although some SP terminals contacted SPR-immunoreactive membrane, no more than 15% of the SPR-laden membrane apposed synaptic terminals [7].

Chemical compound and disease context of Spr


Biological context of Spr


Anatomical context of Spr

  • Light microscopy revealed an excellent correlation between the patterns of SPR immunoreactivity and of 125I-labeled SPR-binding sites in the central nervous system [7].
  • These results suggest that in contrast to more "classical" central and peripheral nervous system synapses, wherein the receptor immediately apposes the site of neurotransmitter storage and release, much of the surface of SPR-expressing neurons can be targeted by SP that diffuses a considerable distance from its site of release [7].
  • The SPR antiserum recognized a broad protein band on Western blots of membranes prepared from cells expressing SPR but not from cells transfected with vector alone [3].
  • Binding of 125I-SPR393-407 to the antiserum was also displaced in a parallel manner by membrane proteins from tissues expressing high levels of the SPR (brain and submaxillary gland) [3].
  • These antibodies can be used to localize the SPR in tissues and cells and to examine the function of the receptor in cell lines [3].

Associations of Spr with chemical compounds

  • In the present study we used an antiserum raised against a synthetic peptide corresponding to the carboxyl-terminal tail of the substance P (SP) receptor (SPR) to further explore the relationship between a neuropeptide and its receptor [7].
  • Second, a chimeric SPR construct of a hydrophilic Flag peptide (DYKDDDDK) genetically engineered in sequence with the extracellular N-terminus of rat SPR was generated by polymerase chain reaction [3].
  • The results suggest that when sepiapterin reductase activity is limiting, a large proportion of BH4 synthesis proceeds through the 6-lactoyl intermediate [13].
  • Further studies with sepiapterin, methotrexate, and N-acetylserotonin (an inhibitor of the BH4 synthetic enzyme, sepiapterin reductase) indicated that the BH4 is synthesized in RASMC predominantly from GTP; however, a lesser amount may derive from pterin salvage [14].
  • Measurements were made of the rate of conversion of 6PPH4, generated from dihydroneopterin triphosphate with purified 6PPH4 synthase, to BH4 in the presence of mixtures of pure sepiapterin reductase and the 6PPH4 (2'-oxo)reductase purified from rat brains [13].

Other interactions of Spr


Analytical, diagnostic and therapeutic context of Spr


  1. Isolation and expression of rat liver sepiapterin reductase cDNA. Citron, B.A., Milstien, S., Gutierrez, J.C., Levine, R.A., Yanak, B.L., Kaufman, S. Proc. Natl. Acad. Sci. U.S.A. (1990) [Pubmed]
  2. The complete amino acid sequence of the mature form of rat sepiapterin reductase. Oyama, R., Katoh, S., Sueoka, T., Suzuki, M., Ichinose, H., Nagatsu, T., Titani, K. Biochem. Biophys. Res. Commun. (1990) [Pubmed]
  3. Characterization of antibodies to the rat substance P (NK-1) receptor and to a chimeric substance P receptor expressed in mammalian cells. Vigna, S.R., Bowden, J.J., McDonald, D.M., Fisher, J., Okamoto, A., McVey, D.C., Payan, D.G., Bunnett, N.W. J. Neurosci. (1994) [Pubmed]
  4. Functional wild-type and carboxyl-terminal-tagged rat substance P receptors expressed in baculovirus-infected insect Sf9 cells. Schreurs, J., Yamamoto, R., Lyons, J., Munemitsu, S., Conroy, L., Clark, R., Takeda, Y., Krause, J.E., Innis, M. J. Neurochem. (1995) [Pubmed]
  5. In vitro and in vivo studies of substance P receptor expression in rats with the new analog [indium-111-DTPA-Arg1]substance P. Breeman, W.A., VanHagen, M.P., Visser-Wisselaar, H.A., van der Pluijm, M.E., Koper, J.W., Setyono-Han, B., Bakker, W.H., Kwekkeboom, D.J., Hazenberg, M.P., Lamberts, S.W., Visser, T.J., Krenning, E.P. J. Nucl. Med. (1996) [Pubmed]
  6. Rapid endocytosis of a G protein-coupled receptor: substance P evoked internalization of its receptor in the rat striatum in vivo. Mantyh, P.W., Allen, C.J., Ghilardi, J.R., Rogers, S.D., Mantyh, C.R., Liu, H., Basbaum, A.I., Vigna, S.R., Maggio, J.E. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  7. Synaptic relationship between substance P and the substance P receptor: light and electron microscopic characterization of the mismatch between neuropeptides and their receptors. Liu, H., Brown, J.L., Jasmin, L., Maggio, J.E., Vigna, S.R., Mantyh, P.W., Basbaum, A.I. Proc. Natl. Acad. Sci. U.S.A. (1994) [Pubmed]
  8. Distribution of SPR-like immunoreactivity in the medullary visceral zone of the rat and changes following acute myocardial ischemia induced by intravenous injection of vasopressin. Gao, W., Liu, H., Rao, Z., Ju, G. Journal für Hirnforschung. (1998) [Pubmed]
  9. Mutational analysis of sites in sepiapterin reductase phosphorylated by Ca2+/calmodulin-dependent protein kinase II. Fujimoto, K., Takahashi, S.Y., Katoh, S. Biochim. Biophys. Acta (2002) [Pubmed]
  10. Quantitative trait loci on chromosomes 1 and 4 affect lipid phenotypes in the rat. Kovács, P., Klöting, I. Arch. Biochem. Biophys. (1998) [Pubmed]
  11. Alleles of the spontaneously hypertensive rat decrease blood pressure at loci on chromosomes 4 and 13. Kovács, P., Voigt, B., Klöting, I. Biochem. Biophys. Res. Commun. (1997) [Pubmed]
  12. Control of cell-cycle-associated tetrahydrobiopterin synthesis in rat thymocytes. Schott, K., Brand, K., Hatakeyama, K., Kagamiyama, H., Maier, J., Werner, T., Ziegler, I. Exp. Cell Res. (1992) [Pubmed]
  13. The biosynthesis of tetrahydrobiopterin in rat brain. Purification and characterization of 6-pyruvoyl tetrahydropterin (2'-oxo)reductase. Milstien, S., Kaufman, S. J. Biol. Chem. (1989) [Pubmed]
  14. Tetrahydrobiopterin synthesis. An absolute requirement for cytokine-induced nitric oxide generation by vascular smooth muscle. Gross, S.S., Levi, R. J. Biol. Chem. (1992) [Pubmed]
  15. Effects of quantitative trait loci for lipid phenotypes in the rat are influenced by age. Kovács, P., van den Brandt, J., Klöting, I. Clin. Exp. Pharmacol. Physiol. (1998) [Pubmed]
  16. Hormonal regulation of guanosine triphosphate cyclohydrolase activity and biopterin levels in the rat adrenal cortex. Abou-Donia, M.M., Duch, D.S., Nichol, C.A., Viveros, O.H. Endocrinology (1983) [Pubmed]
  17. Immunological studies on the participation of 6-pyruvoyl tetrahydropterin (2'-oxo) reductase, an aldose reductase, in tetrahydrobiopterin biosynthesis. Milstien, S., Kaufman, S. Biochem. Biophys. Res. Commun. (1989) [Pubmed]
  18. Regulation of tyrosine hydroxylase and tetrahydrobiopterin biosynthetic enzymes in PC12 cells by NGF, EGF and IFN-gamma. Anastasiadis, P.Z., Kuhn, D.M., Blitz, J., Imerman, B.A., Louie, M.C., Levine, R.A. Brain Res. (1996) [Pubmed]
  19. Immunological evidence for the requirement of sepiapterin reductase for tetrahydrobiopterin biosynthesis in brain. Levine, R.A., Kapatos, G., Kaufman, S., Milstien, S. J. Neurochem. (1990) [Pubmed]
  20. Distribution of trigeminohypothalamic and spinohypothalamic tract neurons displaying substance P receptor-like immunoreactivity in the rat. Li, J.L., Kaneko, T., Shigemoto, R., Mizuno, N. J. Comp. Neurol. (1997) [Pubmed]
  21. Primary afferent fibers that contribute to increased substance P receptor internalization in the spinal cord after injury. Allen, B.J., Li, J., Menning, P.M., Rogers, S.D., Ghilardi, J., Mantyh, P.W., Simone, D.A. J. Neurophysiol. (1999) [Pubmed]
  22. Role of the conserved Ser-Tyr-Lys triad of the SDR family in sepiapterin reductase. Fujimoto, K., Hara, M., Yamada, H., Sakurai, M., Inaba, A., Tomomura, A., Katoh, S. Chem. Biol. Interact. (2001) [Pubmed]
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