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Regulation of the expression of the proenkephalin gene in cultured meningeal fibroblasts: opposite effects of α1- and β2-adrenoceptors

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Abstract

Meningeal fibroblasts express the proenkephalin gene during embryonal development but terminate the expression shortly before birth. When brought into primary culture at postnatal day 1, the fibroblasts again express the gene. Activation of protein kinase A reduces this expression and thus may contribute to its prenatal termination. Since the noradrenergic innervation of the meninges begins around the time of birth, it was investigated in the present study, how adrenergic agonists affected the levels of proenkephalin mRNA in cultured fibroblasts. The β2-adrenoceptor agonists salbutamol and procaterol increased the levels of endogenous cAMP and diminished the concentration of proenkephalin mRNA indicating that the cultured fibroblasts possessed this β-subtype. In contrast, noradrenaline increased the level of proenkephalin mRNA in a concentration-dependent manner. This effect was independent of endogenous cAMP and was mediated by α1-adrenoceptors. The data indicate that the noradrenergic innervation of the meninges at the time of birth is not responsible for the termination of the proenkephalin gene expression.

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References

  • Batter DK, Kessler JA (1991) Region-specific regulation of preproenkephalin mRNA in cultured astrocytes. Mol Brain Res 11:65–69

    Google Scholar 

  • Bayer SA, Altman J, Russo RJ, Dai X, Simmons JA (1991) Cell migration in the rat embryonic neocortex. J Comp Neurol 307:499–516

    Google Scholar 

  • Behar OZ, Ovadia H, Polakiewicz RD, Abramsky O, Rosen H (1991) Regulation of proenkephalin A messenger ribonucleic acid levels in normal B lymphocytes: specific inhibition by glucocorticoid hormones and superinduction by cycloheximide. Endocrinology 129:649–655

    Google Scholar 

  • Berry M, Rogers AW (1965) The migration of neuroblasts in the developing cerebral cortex. J Anat 99:691–709

    Google Scholar 

  • Berry M, Rogers AW, Eayrs JT (1964) Pattern of cell migration during cortical histogenesis. Nature 203:591–593

    Google Scholar 

  • Bilski AJ, Halliday SE, Fitzgerald JD, Wale JL (1983) The pharmacology of a β2-selective adrenoceptor antagonist (ICI 188,551). J Cardiovasc Pharmacol 5:430–437

    Google Scholar 

  • Brittain RT, Farmer JB, Jack D, Martin LE, Simpson WT (1968) α-[(t-butylamino) methyl]-4-hydroxy-m-xylene-α3-diol (AH-3365): a selective β-adrenergic stimulant. Nature 219:862–863

    Google Scholar 

  • Cheley S, Anderson R (1984) A reproducible microanalytical method for the detection of specific RNA sequences by dot-blot hybridization. Anal Biochem 137:15–19

    Google Scholar 

  • Cullum VA, Farmer JB, Jack D, Levy GP (1969) Salbutamol: a new selective β-adrenoceptor stimulant. Br J Pharmacol 35:141–151

    Google Scholar 

  • Ebersolt C, Perez M, Vassent G, Bockaert J (1981) Characteristics of the β1- and β2-adrenergic-sensitive adenylate cyclases in glial cell primary cultures and their comparison with β2-adrenergic-sensitive adenylate cyclase of meningeal cells. Brain Res 213:151–161

    Google Scholar 

  • Eiden LE, Giraud P, Affolter HU, Herbert E, Hotchkiss AJ (1984) Alternative modes of enkephalin biosynthesis regulation by reserpine and cyclic AMP in cultured chromaffin cells. Proc Nail Acad Sci USA 81:3949–3953

    Google Scholar 

  • Hauser KF, McLaughlin PJ, Zagon IS (1987) Endogenous opioids regulate growth and spine formation in developing rat brain. Brain Res 416:157–161

    Google Scholar 

  • Hauser KF, McLaughlin PJ, Zagon IS (1989) Endogenous opioid systems and the regulation of dendritic growth and spine formation. J Comp Neurol 281:13–22

    Google Scholar 

  • Hidaka H, Kobayashi R (1992) Pharmacology of protein kinase inhibitors. Annu Rev Pharmacol Toxicol 32:377–397

    Google Scholar 

  • Hildebrand B, Olenik C, Meyer DK (1995) Rat meningeal fibroblasts in primary culture express the proenkephalin gene. Neuropeptides 29:89–95

    Google Scholar 

  • Höltke H-J, Kessler C (1990) Non-radioactive labeling of RNA transcripts in vitro with the hapten digoxigenin (DIG); hybridization and ELISA-based detection. Nucl Acid Res 18:5843–5851

    Google Scholar 

  • Jonakait GM, Black IB (1989) Regulation of catecholamine development. Handb Exp Pharmacol 90/II:137–179

    Google Scholar 

  • Joshi J, Sabol S (1991) Proenkephalin gene expression in C6 rat glioma cells: potentiation of cyclic adenosine 3′,5′-monophosphate-dependent transcription by glucocorticoids. Mol Endocrinol 5:1069–1080

    Google Scholar 

  • Keshet E, Polakiewicz RD, Itin A, Ornoy A, Rosen H (1989) Proenkephalin A is expressed in mesodermal lineages during organogenesis. EMBO J 8:2917–2923

    Google Scholar 

  • Kilpatrick DL, Millette CF (1986) Expression of proenkephalin messenger RNA by mouse spermatogenic cells. Proc Natl Acad Sci USA 83:5015–5018

    Google Scholar 

  • Kley N (1988) Multiple regulation of proenkephalin gene expression by protein kinase C. J Biol Chem 263:2003–2008

    Google Scholar 

  • Kley N, Loeffler J-P, Pittius CW, Höllt V (1987) Involvement of ion channels in the induction of proenkephalin A gene expression by nicotine and CAMP in bovine chromaffin cells. J Biol Chem 262:4083–4089

    Google Scholar 

  • Kobierski LA, Chu H-M, Tan Y, Comb MJ (1991) cAMP-dependent regulation of proenkephalin by junD and junB: positive and negative effects of AP-1 proteins. Proc Natl Acad Sci USA 88:10222–10226

    Google Scholar 

  • Lehrach H, Diamond D, Wozney JM, Boedtker H (1977) RNA molecular weight determinations by gel electrophoresis under denaturing conditions, a critical reexamination. Biochemistry 16:4743–4751

    Google Scholar 

  • Lemoine H, Ehle B, Kaumann AJ (1985) Direct labelling of β2-adrenoceptors. Comparison of binding potency of 3H-ICI 188,551 and blocking potency of ICI 118,551. Naunyn-Schmiedeberg's Arch Pharmacol 331:40–51

    Google Scholar 

  • Lidow MS, Rakic P (1994) Unique profiles of the α1-, α2-, and β-adrenergic receptors in the developing cortical plate and transient embryonic zones of the rhesus monkey. J Neurosci 14:4064–4078

    Google Scholar 

  • Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193:265–275

    Google Scholar 

  • Melner MH, Low KG, Allen RG, Nielsen CP, Young SL, Saneto RP (1990) The regulation of proenkephalin expression in a distinct population of glial cells. EMBO J 9:791–796

    Google Scholar 

  • Nakaki T, Nakayama M, Yamamoto S, Kato R (1990) α1-adrenergic stimulation and β2-adrenergic inhibition of DNA synthesis in vascular smooth muscle cells. Mol Pharmacol 37:30–36

    Google Scholar 

  • Ortmann R (1978) Effect of PG12 and stable analogues on cyclic nucleotide levels in clonal cell lines of CNS origin. FEBS Lett 90:348–351

    Google Scholar 

  • Polakiewicz DR, Rosen H (1990) Regulated expression of proenkephalin A during ontogenic development of mesenchymal derivative tissue. 10:736–742

    Google Scholar 

  • Rakic P, Lidow MS (1995) Distribution and density of monamine receptors in the primate visual cortex devoid of retinal input from early embryonic stages. J Neurosci 15:2561–2574

    Google Scholar 

  • Rubin E (1985a) Development of the rat superior cervical ganglion: ganglion cell maturation. J Neurosci 5:673–684

    Google Scholar 

  • Rubin E (1985b) Development of the rat superior cervical ganglion: initial stages of synapse formation. J Neurosci 5:697–704

    Google Scholar 

  • Seatriz JV, Hammer RP (1993) Effects of opiates on neuronal development in the rat cerebral cortex. Brain Res Bull 30:523–527

    Google Scholar 

  • Shinoda H, Marini AM, Cosi C, Schwartz JP (1989) Brain region and gene specificity of neuropeptide gene expression in cultured astrocytes. Nature 245:415–417

    Google Scholar 

  • Starke K (1981) α-Adrenoceptor subclassification. Rev Physiol Biochem Pharmacol 88:199–236

    Google Scholar 

  • Starke K (1987) Presynaptic α-autoreceptors. Rev Physiol Biochem Pharmacol 107:74–146

    Google Scholar 

  • Theodoridu A, Olenik C, Boeckh C, Ziefer P, Gebicke-Härter P, Meyer DK (1994) Interaction of protein kinases A and C in their effects on the proenkephalin gene in astroglial cells. Neurochem Int 25:385–393

    Google Scholar 

  • Thomas SA, Matsumoto AM, Palmiter RD (1995) Noradrenaline is essential for mouse fetal development. Nature 374:643–646

    Google Scholar 

  • Weisinger G (1995) The transcriptional regulation of the proenkephalin gene. Biochem J 307:617–629

    Google Scholar 

  • Yabuuchi Y (1977) The β-adrenoceptor stimulant properties of OPC2009 on guinea-pig isolated tracheal, right atria] and left atria] preparations. Br J Pharmacol 61:513–521

    Google Scholar 

  • Yoshikawa K, Sabol S (1986) Glucocorticoid and cyclic AMP synergistically regulate the abundance of proenkephalin messenger RNA in neuroblastoma-glioma hybrid cells. Biochem Biophys Res Commun 139:1–10

    Google Scholar 

  • Yoshikawa K, Williams C, Sabol SL (1984) Rat brain proenkephalin mRNA. J Biol Chem 259:14301–14308

    Google Scholar 

  • Zagon IS, McLaughlin PJ (1983) Increased brain size and cellular content in infant rats treated with an opiate antagonist. Science 221:1179–1180

    Google Scholar 

  • Zagon IS, McLaughlin PJ (1986) Opioid antagonist (naltrexone) modulation of cerebellar development: Histological and morphometric studies. J Neurosci 6:1424–1432

    Google Scholar 

  • Zerkowski H-R, Ikezono K, Rohm N, Reidemeister J-C, Brodde O-E (1986) Human myocardial β-adrenoceptors: demonstration of both β1- and β2-adrenoceptors mediating contractile responses to β-agonists on the isolated right atrium. Naunyn-Schmiedeberg's Arch Pharmacol 332:142–147

    Google Scholar 

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Authors and Affiliations

  1. Department of Pharmacology and Toxicology, University of Freiburg, Hermann Herderstrasse 5, D-79104, Freiburg, Germany

    Brigitte Hildebrand, Bernhard Wissler, Claudia Olenik & Dieter K. Meyer

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  1. Brigitte Hildebrand
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  2. Bernhard Wissler
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  3. Claudia Olenik
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  4. Dieter K. Meyer
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Hildebrand, B., Wissler, B., Olenik, C. et al. Regulation of the expression of the proenkephalin gene in cultured meningeal fibroblasts: opposite effects of α1- and β2-adrenoceptors. Naunyn-Schmiedeberg's Arch Pharmacol 354, 404–410 (1996). https://doi.org/10.1007/BF00168429

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  • DOI: https://doi.org/10.1007/BF00168429

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