Skip to main content
Log in

Differential distribution of calcineurin Aα isoenzyme mRNA's in rat brain

  • Short communications
  • Published:
Naunyn-Schmiedeberg's Archives of Pharmacology Aims and scope Submit manuscript

Summary

Specific antisense oligonucleotide probes for the α isoforms of the catalytic subunit (A-subunit) of calcineurin were prepared and the distribution of Aα 1 and Aα 2 mRNA's has been studied in rat brain using in situ hybridization histochemistry. Clear regional differences have been observed for the Aα 1 and Aα 2 isoforms. The predominant form, Aα 1, was found to be preferentially expressed in the caudate putamen, the pyramidal cell layer of the hippocampus, specific cortical cell layers, the cerebellar granular cell layer and some other brain areas. On the other hand, the Aα 2 isoform, although being generally less abundant than Aα 1, gave an intense autoradiography signal in the dentate gyrus of the hippocampus and was the major transcript in the amygdala, the superior and the inferior colliculus, the central gray matter and the reticular formation. These regional differences might reflect specific functions exerted by the two alternatively spliced isoenzymes in the CNS and opens the perspective of interfering with defined Cacineurin-dependent signal transduction pathways using isoform-specific compounds.

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

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

References

  • Armstrong DL (1989) Calcium channel regulation by calcineurin, a Ca2+-activated phosphatase in mammalian brain. Trends Neurosci 12:117–122

    Google Scholar 

  • Catania MV, Aronica E, Sortino MA, Canonico PL, Nicoletti F (1991) Desensitization of metabotropic glutamate receptors in neuronal cultures. J Neurochem 56:1329–1335

    Google Scholar 

  • Chen QX, Steltzer A, Kay AR, Wong RKS (1990) GABA(A) receptor function is regulated by phosphorylation in acutely dissociated guinea-pig hippocampal neurons. J Physiol 420:207–221

    Google Scholar 

  • Guerini D, Klee CB (1989) Cloning of human calcineurin A: evidence for two isoenzymes and identification of a polyproline structural domain. Proc Natl Acad Sci USA 86:9183–9187

    Google Scholar 

  • Halpain S, Girault JA, Greengard P (1990) Activation of NMDA receptors induces phosphorylation of DARPP-32 in rat striatal slices. Nature 343:369–372

    Google Scholar 

  • Hashimoto Y, Perrino BA, Soderling TR (1990) Identification of an autoinhibitory domain in calcineurin. J Biol Chem 265:1924–1927

    Google Scholar 

  • Ito A, Hashimoto T, Hirai M, Takeda T, Shuntoh H, Kuno T, Tanaka C (1989) The complete primary structure of calcineurin A, a calmodulin binding protein homologous with protein phosphatases 1 and 2A. Biochem Biophys Res Commun 163:1492–1497

    Google Scholar 

  • Kincaid RL, Giri PR, Higuchi S, Tamura J, Dixon SC, Marietta CA, Amorese DA, Martin BM (1990) Cloning and characterization of molecular isoforms of the catalytic subunit of calcineurin using non-isotopic methods. J Biol Chem 265:11312–11319

    Google Scholar 

  • King MM, Huang CY, Chock PB, Nairn AC, Hemmings Jr HC, Chan J, Greengard P (1984) Mammalian phosphoproteins as substrates for calcineurin. J Biol Chem 259:8080–8083

    Google Scholar 

  • Klee CB, Crouch TM, Krinks MM (1979) Calcineurin: calcium- and calmodulin-binding protein of the nervous system. Proc Natl Acad Sci USA 84:1118–1122

    Google Scholar 

  • Kuno T, Takeda T, Hirai M, Ito A, Mukai H (1989) Evidence for a second isoform of the catalytic subunit of calmodulin-dependent phosphatase (calcineurin). Biochem Biophys Res Commun 165: 1352–1358

    Google Scholar 

  • Liu J (1993) FK506 and cyclosporin: Molecular probes for studying intracellular signal transduction. Trends Pharmacol Sci 14:182–189

    Google Scholar 

  • Liu J, Farmer JD, Lane WS, Friedman J, Weissman I, Schreiber SL (1991) Calcineurin is a common target of cyclophylin-cyclosporin A and FKBP-FK-506 complexes. Cell 66:807–815

    Google Scholar 

  • Massieu L, Rocamura N, Palacios JM, Boddeke HWGM (1992) Administration of quinolinic acid in the rat hippocampus induces expression of c-fos and NGFI-A. Mol Brain Res 16:88–96

    Google Scholar 

  • Miyamoto E (1991) Rat mRNA for calcineurin A. Genbank accession number X57115

  • Polli JW, Billingsley ML, Kincaid RL (1991) Expression of the calmodulin-dependent protein phosphatase, calcineurin, in rat brain: development patterns and the role of nigrostriatal innervation. Dev Brain Res 63:105–119

    Google Scholar 

  • Sakuta H, Sekiguchi M, Okamoto K, Sakai Y (1991) Oscillatory muscarinic acetylcholine responses of Xenopus oocytes are desensitized by protein kinase C and sensitized by protein phosphatase 2B. Eur J Pharmacol, Mol Pharmacol Sect 208:297–305

    Google Scholar 

  • Steiner JP, Dawson TM, Fotuhi M, Glatt CE, Snowman AM, Cohen N, Snyder SH (1992) High brain densities of the immunophilin FKBP colocalized with calcineurin. Nature 358:584–587

    Google Scholar 

  • Takaishi T, Saito N, Kuno T, Tanaka C (1991) Differential distribution of the mRNA encoding two isoforms of the catalytic subunit of calcineurin in the rat brain. Biochem Biophys Res Commun 174:393–398

    Google Scholar 

  • Yeats JC, Boddeke HWGM, Docherty RJ (1992) Capsaicin desensitization in rat dorsal root ganglion neurones is due to activation of calcineurin. Br J Pharmacol 107 [Suppl]:238P

Download references

Author information

Authors and Affiliations

Authors

Additional information

Correspondence to: H. Boddeke at the above address

Rights and permissions

Reprints and permissions

About this article

Cite this article

Buttini, M., Limonta, S., Luyten, M. et al. Differential distribution of calcineurin Aα isoenzyme mRNA's in rat brain. Naunyn-Schmiedeberg's Arch Pharmacol 348, 679–683 (1993). https://doi.org/10.1007/BF00167247

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00167247

Key words

Navigation