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Sptan1  -  spectrin, alpha, non-erythrocytic 1

Rattus norvegicus

Synonyms: A2a, Alpha-II spectrin, Fodrin alpha chain, IPF, Spectrin alpha chain, non-erythrocytic 1, ...
 
 
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Disease relevance of Spna2

  • RESULTS: Administration of a selective A1 agonist induced hyperamylasemia and morphologic changes in the pancreas characterized by interstitial edema and leukocyte infiltration; neither A2a nor A3 agonist produced such changes [1].
  • We have previously reported that phosphorylation of adenylyl cyclase type VI (AC6) may result in the suppression of adenylyl cyclase activity during desensitization of the A2a-adenosine receptor-mediated cAMP response (A2a desensitization) in rat pheochromocytoma PC12 cells [2].
  • Idiopathic pulmonary fibrosis (IPF; a progressive lung disease) is characterized by parenchymal remodeling with enlarged air spaces called honeycomb cysts and palisades of fibroblasts called fibroblast foci [3].
  • Using explanted rat lung slices, we transfected alveolar epithelial cells with the retrovirus pMX containing a site-directed mutation in which Cys223 and Cys225 were substituted with serines, resulting in release of biologically active TGF-beta1 and fibroblast proliferation and remodeling that resembled IPF [3].
  • The A2a agonist 2-hexynyl-5'-N-ethylcarboxamidoadenosine induced dose-related hypotension (eg, 0.003 mg/kg; peak, -36 mm Hg; time to peak, 0.32 hour) with reflex tachycardia (eg, 0.003 mg/kg; peak, 152 bpm; time to peak, 0.35 hour) [4].
 

Psychiatry related information on Spna2

  • Since high-affinity adenosine A2 receptors (A2a) are localized exclusively in dopamine-rich regions in the central nervous system and mediate inhibition of locomotor activity, we have examined the effect of A2a receptor activation on D1 and D2 receptor binding in membrane preparations of the rat striatum [5].
  • The A2a receptor agonist, CGS 21680, was one order of magnitude more potent than the A1 receptor agonist, cyclohexaladenosine, in inducing rapid eye movement sleep increases [6].
  • The authors tested in rats the hypothesis that potentiating effects of sleep deprivation on LORR can be altered by adenosine A1 and A2a receptor antagonists [7].
 

High impact information on Spna2

 

Chemical compound and disease context of Spna2

 

Biological context of Spna2

  • Tyrosine phosphorylation regulates alpha II spectrin cleavage by calpain [13].
  • Yeast two-hybrid screening of a kidney cDNA library revealed that the SH3 domain of alpha II-spectrin binds specifically isoform A of low-molecular-weight phosphotyrosine phosphatase (LMW-PTP) [13].
  • Thus, stimulation of A2a receptors potently reduces the affinity of D2 agonist binding sites within the plasma membrane of striatal neurons [5].
  • Analysis of spontaneous miniature inhibitory synaptic currents indicated that suppression of intrastriatal GABAergic synaptic transmission was attributable to presynaptic, but not postsynaptic, A2a receptors [14].
  • Our data suggest that inhibition of adenylyl cyclase after short-term agonist treatment, down-regulation of Gs alpha protein level after long-term agonist treatment, and activation of PDE after long-term agonist treatment account for desensitization of the A2a-mediated response in PC12 cells [9].
 

Anatomical context of Spna2

 

Associations of Spna2 with chemical compounds

  • Western blotting showed that alpha II-spectrin is tyrosine phosphorylated in vivo [13].
  • These regions also have the highest density of adenosine A2a receptors (A2a) in the brain [19].
  • The A2a agonist 2-[p-(2-carboxyethyl)phenethylamino]-5'- N-ethylcarboxamidoadenosine (CGS 21680) increased the Kd of the dopamine D2 agonist L-(-)-N-[3H]propylnorapomorphine without affecting the Bmax [5].
  • Reversible inhibition of forskolin-evoked adenylyl cyclase activity in desensitized cells occurred after incubation with an A2a-selective adenosine agonist (CGS21680) [20].
  • Regulation of adenylyl cyclase type VI activity during desensitization of the A2a adenosine receptor-mediated cyclic AMP response: role for protein phosphatase 2A [20].
 

Enzymatic interactions of Spna2

 

Other interactions of Spna2

  • As we have previously demonstrated, cleavage of alpha II-spectrin by calpain and caspase-3 results in accumulation of protease-specific spectrin breakdown products (SBDPs) that can be used to monitor the magnitude and temporal duration of protease activation [21].
  • Using a novel ischemia-induced substrate cleavage biochemical approach, spectrin P120 fragment, a caspase-specific cleavage product of alpha II spectrin, a cytoskeletal protein, was shown to be elevated by western blotting [22].
 

Analytical, diagnostic and therapeutic context of Spna2

  • Partial sequence analysis shows that IPF alpha is derived from alpha fodrin, a protein implicated in several diverse cellular activities [8].
  • In situ hybridization histochemistry was used either in combination with retrograde labeling of striatonigral neurons to determine the projection site of A2a receptor expressing neurons, or on consecutive thin sections to address the putative coexpression of the A2a receptor with the D1 or D2 receptors in individual neurons [15].
  • Photoaffinity labeling with 2(-)[2-(4-azido-3(-)[125I]- iodophenyl)ethylamino]adenosine and autoradiography with 2(-)[2-(4-amino-3(-)[125I]iodophenyl)ethylamino]adenosine of A2a adenosine receptors in rat brain [23].
  • 2. Three groups of normotensive conscious rats received an short intravenous infusion of 1.4 mg kg-1 CADO during constant infusions of the A1-selective antagonist, 8-cyclopentyltheophylline (CPT; 20 micrograms min-1 kg-1), the A2a-selective antagonist, 8-(3-chlorostyryl) caffeine (CSC; 32 micrograms min-1 kg-1) or the vehicle [24].
  • Each experiment tested a specific dose of an A1 receptor antagonist (8-cyclopentyltheophylline given via microinjection into the basal forebrain), an A2a receptor antagonist (ZM241385 via intraperitoneal administration), or both [7].

References

  1. Activation of adenosine A1-receptor pathway induces edema formation in the pancreas of rats. Satoh, A., Shimosegawa, T., Satoh, K., Ito, H., Kohno, Y., Masamune, A., Fujita, M., Toyota, T. Gastroenterology (2000) [Pubmed]
  2. Protein kinase C inhibits adenylyl cyclase type VI activity during desensitization of the A2a-adenosine receptor-mediated cAMP response. Lai, H.L., Yang, T.H., Messing, R.O., Ching, Y.H., Lin, S.C., Chern, Y. J. Biol. Chem. (1997) [Pubmed]
  3. Proliferation of pulmonary interstitial fibroblasts is mediated by transforming growth factor-beta1-induced release of extracellular fibroblast growth factor-2 and phosphorylation of p38 MAPK and JNK. Khalil, N., Xu, Y.D., O'Connor, R., Duronio, V. J. Biol. Chem. (2005) [Pubmed]
  4. Modeling hemodynamic profiles by telemetry in the rat. A study with A1 and A2a adenosine agonists. Bonizzoni, E., Milani, S., Ongini, E., Casati, C., Monopoli, A. Hypertension (1995) [Pubmed]
  5. Stimulation of high-affinity adenosine A2 receptors decreases the affinity of dopamine D2 receptors in rat striatal membranes. Ferre, S., von Euler, G., Johansson, B., Fredholm, B.B., Fuxe, K. Proc. Natl. Acad. Sci. U.S.A. (1991) [Pubmed]
  6. Enhancement of rapid eye movement sleep in the rat by actions at A1 and A2a adenosine receptor subtypes with a differential sensitivity to atropine. Marks, G.A., Shaffery, J.P., Speciale, S.G., Birabil, C.G. Neuroscience (2003) [Pubmed]
  7. Effect of sleep deprivation on righting reflex in the rat is partially reversed by administration of adenosine A1 and A2 receptor antagonists. Tung, A., Herrera, S., Szafran, M.J., Kasza, K., Mendelson, W.B. Anesthesiology (2005) [Pubmed]
  8. A protein factor that inhibits ATP-dependent glutamate and gamma-aminobutyric acid accumulation into synaptic vesicles: purification and initial characterization. Ozkan, E.D., Lee, F.S., Ueda, T. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  9. Multiple mechanisms for desensitization of A2a adenosine receptor-mediated cAMP elevation in rat pheochromocytoma PC12 cells. Chern, Y., Lai, H.L., Fong, J.C., Liang, Y. Mol. Pharmacol. (1993) [Pubmed]
  10. Inhibition of caffeine-induced Ca2+ release by adenosine in mammalian skinned slow- and fast-twitch fibres. Hleihel, W., Talon, S., Huchet-Cadiou, C., Léoty, C. Naunyn Schmiedebergs Arch. Pharmacol. (2001) [Pubmed]
  11. Differing roles of adenosine receptor subtypes in retinal ischemia-reperfusion injury in the rat. Li, B., Rosenbaum, P.S., Jennings, N.M., Maxwell, K.M., Roth, S. Exp. Eye Res. (1999) [Pubmed]
  12. The adenosine receptor agonist, APNEA, increases calcium influx into rat cortical synaptosomes through N-type channels associated with A2a receptors. Li, S.N., Wong, P.T. Neurochem. Res. (2000) [Pubmed]
  13. Tyrosine phosphorylation regulates alpha II spectrin cleavage by calpain. Nicolas, G., Fournier, C.M., Galand, C., Malbert-Colas, L., Bournier, O., Kroviarski, Y., Bourgeois, M., Camonis, J.H., Dhermy, D., Grandchamp, B., Lecomte, M.C. Mol. Cell. Biol. (2002) [Pubmed]
  14. The role of adenosine A2a receptors in regulating GABAergic synaptic transmission in striatal medium spiny neurons. Mori, A., Shindou, T., Ichimura, M., Nonaka, H., Kase, H. J. Neurosci. (1996) [Pubmed]
  15. Adenosine A2 receptors regulate the gene expression of striatopallidal and striatonigral neurons. Schiffmann, S.N., Vanderhaeghen, J.J. J. Neurosci. (1993) [Pubmed]
  16. Region-specific alterations of adenosine receptors expression level in kidney of diabetic rat. Pawelczyk, T., Grden, M., Rzepko, R., Sakowicz, M., Szutowicz, A. Am. J. Pathol. (2005) [Pubmed]
  17. Adenosine-A2a receptor down-regulates cerebral smooth muscle L-type Ca2+ channel activity via protein tyrosine phosphatase, not cAMP-dependent protein kinase. Murphy, K., Gerzanich, V., Zhou, H., Ivanova, S., Dong, Y., Hoffman, G., West, G.A., Winn, H.R., Simard, J.M. Mol. Pharmacol. (2003) [Pubmed]
  18. 2-Substitution of N6-benzyladenosine-5'-uronamides enhances selectivity for A3 adenosine receptors. Kim, H.O., Ji, X.D., Siddiqi, S.M., Olah, M.E., Stiles, G.L., Jacobson, K.A. J. Med. Chem. (1994) [Pubmed]
  19. Adenosine A2a blockade prevents synergy between mu-opiate and cannabinoid CB1 receptors and eliminates heroin-seeking behavior in addicted rats. Yao, L., McFarland, K., Fan, P., Jiang, Z., Ueda, T., Diamond, I. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  20. Regulation of adenylyl cyclase type VI activity during desensitization of the A2a adenosine receptor-mediated cyclic AMP response: role for protein phosphatase 2A. Chern, Y., Chiou, J.Y., Lai, H.L., Tsai, M.H. Mol. Pharmacol. (1995) [Pubmed]
  21. Accumulation of non-erythroid alpha II-spectrin and calpain-cleaved alpha II-spectrin breakdown products in cerebrospinal fluid after traumatic brain injury in rats. Pike, B.R., Flint, J., Dutta, S., Johnson, E., Wang, K.K., Hayes, R.L. J. Neurochem. (2001) [Pubmed]
  22. Immunohistochemical and biochemical assessment of caspase-3 activation and DNA fragmentation following transient focal ischemia in the rat. Davoli, M.A., Fourtounis, J., Tam, J., Xanthoudakis, S., Nicholson, D., Robertson, G.S., Ng, G.Y., Xu, D. Neuroscience (2002) [Pubmed]
  23. Photoaffinity labeling with 2(-)[2-(4-azido-3(-)[125I]- iodophenyl)ethylamino]adenosine and autoradiography with 2(-)[2-(4-amino-3(-)[125I]iodophenyl)ethylamino]adenosine of A2a adenosine receptors in rat brain. Luthin, D.R., Lee, K.S., Okonkwo, D., Zhang, P., Linden, J. J. Neurochem. (1995) [Pubmed]
  24. Pharmacokinetic-haemodynamic relationships of 2-chloroadenosine at adenosine A1 and A2a receptors in vivo. Mathoôt, R.A., Soudijn, W., Breimer, D.D., Ijzerman, A.P., Danhof, M. Br. J. Pharmacol. (1996) [Pubmed]
 
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