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Gene Review

Asip  -  agouti signaling protein

Rattus norvegicus

Synonyms: ASP, Agouti switch protein, Agouti-signaling protein
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Disease relevance of A


Psychiatry related information on A


High impact information on A


Chemical compound and disease context of A


Biological context of A

  • Ghrelin (500 nM), agouti-related peptide (1 microM); cocaine and amphetamine-related transcript (500 nM) and leptin (500 nM and 1 microM) did not modulate the firing rate and membrane potential of VTA neurons [21].
  • Since present evidence suggests that poor debrisoquine hydroxylators are at risk, we designed an experimental study comparing its neurotoxic effects in dark Agouti (DA) rats, with poor hydroxylation of debrisoquine with that in Sprague Dawley (SD) rats, which are vigorous hydroxylators [22].
  • The O-desmethyl and 5-hydroxy metabolites are deficient in poor metabolizers of debrisoquine and sparteine and the Dark Agouti rat model of this human phenotype [23].
  • Here, intraperitoneal infusion of a Lewis-derived rat MHC class I molecule, RT1.A(l)-Fc, in Dark Agouti (RT1.A(a)) recipient rats prolonged cardiac graft survival, which led to permanent engraftment [24].
  • To identify additional hypothalamic systems that might be important in mediating the increase in food intake and alterations in energy homeostasis during lactation, the present studies examined the expression of agouti-related protein (AGRP), a recently described homologue of the skin agouti protein [25].

Anatomical context of A

  • In the Dark Agouti rat, active immunization with native BTN triggers an inflammatory response in the CNS characterized by the formation of scattered meningeal and perivascular infiltrates of T cells and macrophages [26].
  • Moreover, this obese model showed an increase in the mRNA expression of cocaine- and amphetamine-regulated transcript, neuropeptide Y and agouti-related protein in the hypothalamic arcuate nucleus (ARC) [5].
  • Agouti-related protein (Agrp) is present in rat and human hypothalamus and is structurally related to agouti protein [27].
  • Detailed double labeling studies in the paraventricular hypothalamic nucleus demonstrated that GALP-containing fibers converged in a more rostral direction than did agouti-related protein-containing fibers [28].
  • In the donor-recipient strain combination Lewis (RT1l) to Dark Agouti (RT1a), indefinite renal allograft survival (MST greater than 100 days) was induced by pretreating recipient animals i.v. with 10(6) to 10(8) viable spleen lymphocytes, seven days before transplantation [29].

Associations of A with chemical compounds


Regulatory relationships of A


Other interactions of A

  • Melanocortin-4 receptor (MC4-R) density is thought to be regulated by synaptic availability of endogenous agonist, alpha-melanocyte-stimulating hormone (alpha-MSH), and also by agouti-related protein (AGRP), which acts as a competitive antagonist [38].
  • In this study, we examined whether ghrelin could stimulate GH secretion and feeding in chronic GHRH, neuropeptide Y, and agouti-related protein deficient rats that were neonatally treated with monosodium glutamate (MSG), which destroys the neurons in the hypothalamic arcuate nucleus (ARC) [39].
  • Agouti-related peptide, neuropeptide Y, and somatostatin-producing neurons are targets for ghrelin actions in the rat hypothalamus [40].
  • Increased Hsp27-immunoreactivity exclusively in the examined cortical areas reveals that Hsp27 is a sensitive marker of astroglial response to the effects of MDMA in these regions of Dark Agouti rat brain and suggests differential responses in astroglial Hsp27-expression between distinct brain areas [41].
  • Melanocortin restraint is exerted through alpha-melanocortin-stimulating hormone derived from proopiomelanocortin (POMC) and is antagonized by agouti-related peptide produced in neurons located in the arcuate nucleus (ARC) [42].

Analytical, diagnostic and therapeutic context of A


  1. Thyroid hormone administration enhances remyelination in chronic demyelinating inflammatory disease. Fernandez, M., Giuliani, A., Pirondi, S., D'Intino, G., Giardino, L., Aloe, L., Levi-Montalcini, R., Calzà, L. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  2. Decreased expression of liver glutathione peroxidase in Long-Evans cinnamon mutant rats predisposed to hepatitis and hepatoma. Suemizu, H., Yoshimura, S., Takeichi, N., Moriuchi, T. Hepatology (1994) [Pubmed]
  3. Chronic central infusion of ghrelin increases hypothalamic neuropeptide Y and Agouti-related protein mRNA levels and body weight in rats. Kamegai, J., Tamura, H., Shimizu, T., Ishii, S., Sugihara, H., Wakabayashi, I. Diabetes (2001) [Pubmed]
  4. Dynamics of early synovial cytokine expression in rodent collagen-induced arthritis : a therapeutic study using a macrophage-deactivating compound. Palmblad, K., Erlandsson-Harris, H., Tracey, K.J., Andersson, U. Am. J. Pathol. (2001) [Pubmed]
  5. A possible role of neuropeptide Y, agouti-related protein and leptin receptor isoforms in hypothalamic programming by perinatal feeding in the rat. López, M., Seoane, L.M., Tovar, S., García, M.C., Nogueiras, R., Diéguez, C., Señarís, R.M. Diabetologia (2005) [Pubmed]
  6. Central administration of ghrelin and agouti-related protein (83-132) increases food intake and decreases spontaneous locomotor activity in rats. Tang-Christensen, M., Vrang, N., Ortmann, S., Bidlingmaier, M., Horvath, T.L., Tschöp, M. Endocrinology (2004) [Pubmed]
  7. Dextrorotatory opioids induce stereotyped behavior in Sprague-Dawley and Dark Agouti rats. Ishmael, J.E., Franklin, P.H., Murray, T.F. Psychopharmacology (Berl.) (1998) [Pubmed]
  8. Functional analysis of the Ala67Thr polymorphism in agouti related protein associated with anorexia nervosa and leanness. de Rijke, C.E., Jackson, P.J., Garner, K.M., van Rozen, R.J., Douglas, N.R., Kas, M.J., Millhauser, G.L., Adan, R.A. Biochem. Pharmacol. (2005) [Pubmed]
  9. Differential regulation of agouti-related protein and neuropeptide Y in hypothalamic neurons following a stressful event. Kas, M.J., Bruijnzeel, A.W., Haanstra, J.R., Wiegant, V.M., Adan, R.A. J. Mol. Endocrinol. (2005) [Pubmed]
  10. Glucose injection reduces neuropeptide Y and agouti-related protein expression in the arcuate nucleus: a possible physiological role in eating behavior. Chang, G.Q., Karatayev, O., Davydova, Z., Wortley, K., Leibowitz, S.F. Brain Res. Mol. Brain Res. (2005) [Pubmed]
  11. The activation status of neuroantigen-specific T cells in the target organ determines the clinical outcome of autoimmune encephalomyelitis. Kawakami, N., Lassmann, S., Li, Z., Odoardi, F., Ritter, T., Ziemssen, T., Klinkert, W.E., Ellwart, J.W., Bradl, M., Krivacic, K., Lassmann, H., Ransohoff, R.M., Volk, H.D., Wekerle, H., Linington, C., Flügel, A. J. Exp. Med. (2004) [Pubmed]
  12. N-acetylglucosaminyltransferase III and V messenger RNA levels in LEC rats during hepatocarcinogenesis. Miyoshi, E., Nishikawa, A., Ihara, Y., Gu, J., Sugiyama, T., Hayashi, N., Fusamoto, H., Kamada, T., Taniguchi, N. Cancer Res. (1993) [Pubmed]
  13. Cytochrome P450 isozymes catalyzing 4-hydroxylation of parkinsonism-related compound 1,2,3,4-tetrahydroisoquinoline in rat liver microsomes. Suzuki, T., Fujita, S., Narimatsu, S., Masubuchi, Y., Tachibana, M., Ohta, S., Hirobe, M. FASEB J. (1992) [Pubmed]
  14. Osteoprotegerin reduces osteoclast numbers and prevents bone erosion in collagen-induced arthritis. Romas, E., Sims, N.A., Hards, D.K., Lindsay, M., Quinn, J.W., Ryan, P.F., Dunstan, C.R., Martin, T.J., Gillespie, M.T. Am. J. Pathol. (2002) [Pubmed]
  15. Effects of chronic central nervous system administration of agouti-related protein in pair-fed animals. Small, C.J., Kim, M.S., Stanley, S.A., Mitchell, J.R., Murphy, K., Morgan, D.G., Ghatei, M.A., Bloom, S.R. Diabetes (2001) [Pubmed]
  16. Ribavirin reduces clinical signs and pathological changes of experimental autoimmune encephalomyelitis in Dark Agouti rats. Milicevic, I., Pekovic, S., Subasic, S., Mostarica-Stojkovic, M., Stosic-Grujicic, S., Medic-Mijacevic, L., Pejanovic, V., Rakic, L., Stojiljkovic, M. J. Neurosci. Res. (2003) [Pubmed]
  17. Glutamate ameliorates experimental vincristine neuropathy. Boyle, F.M., Wheeler, H.R., Shenfield, G.M. J. Pharmacol. Exp. Ther. (1996) [Pubmed]
  18. Thyroid status regulates CART but not AgRP mRNA levels in the rat hypothalamus. López, M., Seoane, L., Tovar, S., Señarís, R.M., Diéguez, C. Neuroreport (2002) [Pubmed]
  19. Function of neuropeptide Y and agouti-related protein at weaning: relation to corticosterone, dietary carbohydrate and body weight. Leibowitz, S.F., Sepiashvili, K., Akabayashi, A., Karatayev, O., Davydova, Z., Alexander, J.T., Wang, J., Chang, G.Q. Brain Res. (2005) [Pubmed]
  20. Acute toxicity of 3,4-methylenedioxymethamphetamine (MDMA) in Sprague-Dawley and Dark Agouti rats. Malpass, A., White, J.M., Irvine, R.J., Somogyi, A.A., Bochner, F. Pharmacol. Biochem. Behav. (1999) [Pubmed]
  21. Effects of arousal- and feeding-related neuropeptides on dopaminergic and GABAergic neurons in the ventral tegmental area of the rat. Korotkova, T.M., Brown, R.E., Sergeeva, O.A., Ponomarenko, A.A., Haas, H.L. Eur. J. Neurosci. (2006) [Pubmed]
  22. Perhexiline-induced lipidosis in the dark Agouti (DA) rat. An animal model of genetically determined neurotoxicity. Meier, C., Wahllaender, A., Hess, C.W., Preisig, R. Brain (1986) [Pubmed]
  23. Methoxyphenamine O-demethylase and 5-hydroxylase: a GLC-ECD assay to study their activities and their inhibition by debrisoquine and sparteine. Hawes, E.M., Roy, S.D., McKay, G., Midha, K.K. Pharmacol. Ther. (1987) [Pubmed]
  24. Recombinant dimeric MHC antigens protect cardiac allografts from rejection and visualize alloreactive T cells. Fried, A., Berg, M., Sharma, B., Bonde, S., Zavazava, N. J. Leukoc. Biol. (2005) [Pubmed]
  25. Altered expression of agouti-related protein and its colocalization with neuropeptide Y in the arcuate nucleus of the hypothalamus during lactation. Chen, P., Li, C., Haskell-Luevano, C., Cone, R.D., Smith, M.S. Endocrinology (1999) [Pubmed]
  26. Butyrophilin, a milk protein, modulates the encephalitogenic T cell response to myelin oligodendrocyte glycoprotein in experimental autoimmune encephalomyelitis. Stefferl, A., Schubart, A., Storch2, M., Amini, A., Mather, I., Lassmann, H., Linington, C. J. Immunol. (2000) [Pubmed]
  27. A C-terminal fragment of Agouti-related protein increases feeding and antagonizes the effect of alpha-melanocyte stimulating hormone in vivo. Rossi, M., Kim, M.S., Morgan, D.G., Small, C.J., Edwards, C.M., Sunter, D., Abusnana, S., Goldstone, A.P., Russell, S.H., Stanley, S.A., Smith, D.M., Yagaloff, K., Ghatei, M.A., Bloom, S.R. Endocrinology (1998) [Pubmed]
  28. Distribution of galanin-like peptide in the rat brain. Takatsu, Y., Matsumoto, H., Ohtaki, T., Kumano, S., Kitada, C., Onda, H., Nishimura, O., Fujino, M. Endocrinology (2001) [Pubmed]
  29. Abrogation of the immunosuppressive effect of donor spleen cells on renal allografts in the rat by irradiation or heat treatment. Cranston, D., Wood, K.J., Morris, P.J. Transplantation (1986) [Pubmed]
  30. Protection against 3,4-methylenedioxymethamphetamine-induced neurodegeneration produced by glutathione depletion in rats is mediated by attenuation of hyperthermia. O'Shea, E., Easton, N., Fry, J.R., Green, A.R., Marsden, C.A. J. Neurochem. (2002) [Pubmed]
  31. Genetic differences in spatial learning between Dark Agouti and Sprague-Dawley strains: possible correlation with the CYP2D2 polymorphism in rats treated neonatally with methamphetamine. Vorhees, C.V., Morford, L.L., Inman, S.L., Reed, T.M., Schilling, M.A., Cappon, G.D., Moran, M.S., Nebert, D.W. Pharmacogenetics (1999) [Pubmed]
  32. Diurnal rhythm of agouti-related protein and its relation to corticosterone and food intake. Lu, X.Y., Shieh, K.R., Kabbaj, M., Barsh, G.S., Akil, H., Watson, S.J. Endocrinology (2002) [Pubmed]
  33. Molecular basis of the Dark Agouti rat drug oxidation polymorphism: importance of CYP2D1 and CYP2D2. Yamamoto, Y., Tasaki, T., Nakamura, A., Iwata, H., Kazusaka, A., Gonzalez, F.J., Fujita, S. Pharmacogenetics (1998) [Pubmed]
  34. Neuromedin s is a novel anorexigenic hormone. Ida, T., Mori, K., Miyazato, M., Egi, Y., Abe, S., Nakahara, K., Nishihara, M., Kangawa, K., Murakami, N. Endocrinology (2005) [Pubmed]
  35. Postnatal development of the hypothalamic neuropeptide Y system. Grove, K.L., Allen, S., Grayson, B.E., Smith, M.S. Neuroscience (2003) [Pubmed]
  36. Possible involvement of c-myc but not ras genes in hepatocellular carcinomas developing after spontaneous hepatitis in LEC rats. Fujimoto, Y., Ishizaka, Y., Tahira, T., Sone, H., Takahashi, H., Enomoto, K., Mori, M., Sugimura, T., Nagao, M. Mol. Carcinog. (1991) [Pubmed]
  37. Agouti-related peptide prevents steroid-induced luteinizing hormone and prolactin surges in female rats. Schioth, H.B., Kakizaki, Y., Kohsaka, A., Suda, T., Watanobe, H. Neuroreport (2001) [Pubmed]
  38. Changes in hypothalamic agouti-related protein (AGRP), but not alpha-MSH or pro-opiomelanocortin concentrations in dietary-obese and food-restricted rats. Harrold, J.A., Williams, G., Widdowson, P.S. Biochem. Biophys. Res. Commun. (1999) [Pubmed]
  39. Ghrelin stimulates GH but not food intake in arcuate nucleus ablated rats. Tamura, H., Kamegai, J., Shimizu, T., Ishii, S., Sugihara, H., Oikawa, S. Endocrinology (2002) [Pubmed]
  40. Agouti-related peptide, neuropeptide Y, and somatostatin-producing neurons are targets for ghrelin actions in the rat hypothalamus. Seoane, L.M., López, M., Tovar, S., Casanueva, F.F., Señarís, R., Diéguez, C. Endocrinology (2003) [Pubmed]
  41. Damage of serotonergic axons and immunolocalization of Hsp27, Hsp72, and Hsp90 molecular chaperones after a single dose of MDMA administration in Dark Agouti rat: temporal, spatial, and cellular patterns. Adori, C., Andó, R.D., Kovács, G.G., Bagdy, G. J. Comp. Neurol. (2006) [Pubmed]
  42. Melanocortin signaling is decreased during neurotoxin-induced transient hyperphagia and increased body-weight gain. Dube, M.G., Pu, S., Kalra, S.P., Kalra, P.S. Peptides (2000) [Pubmed]
  43. Nitric oxide production during adjuvant-induced and collagen-induced arthritis. Cannon, G.W., Openshaw, S.J., Hibbs, J.B., Hoidal, J.R., Huecksteadt, T.P., Griffiths, M.M. Arthritis Rheum. (1996) [Pubmed]
  44. Crosstalk of endothelin-1 and platelet-derived growth factor in cardiac allograft arteriosclerosis. Sihvola, R.K., Pulkkinen, V.P., Koskinen, P.K., Lemström, K.B. J. Am. Coll. Cardiol. (2002) [Pubmed]
  45. Potential of allospecific gene-engineered T cells in transplantation gene therapy: specific T cell activation determines transgene expression in vitro and in vivo. Hammer, M.H., Flügel, A., Seifert, M., Lehmann, M., Brandt, C., Volk, H.D., Ritter, T. Hum. Gene Ther. (2000) [Pubmed]
  46. Specific suppression of interleukin 2 biosynthesis by synthetic antisense oligodeoxynucleotides does not influence allograft rejection. Yun, S., Sawyer, G.J., Zhang, X., Gustafsson, K., Fabre, J.W. Transplantation (2000) [Pubmed]
  47. A short course of cyclosporine immunosuppression inhibits rejection but not tolerance of rat liver allografts. Huang, W.H., Yan, Y., De Boer, B., Bishop, G.A., House, A.K. Transplantation (2003) [Pubmed]
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