Skip to main content
Log in

Norepinephrine-stimulated inositol phospholipid breakdown in the rat cerebral cortex following serotoninergic lesion

  • Original Papers
  • Published:
Journal of Neural Transmission Aims and scope Submit manuscript

Summary

Norepinephrine (NE)-stimulated inositol phospholipid hydrolysis (“PI breakdown”) in rat cerebral cortical miniprisms was used as a measure of alpha1-adrenoceptor function following serotonin and/or NE depletion. The use of ascorbic acid to prevent autooxidation of the NE during the PI breakdown assay was found to be warranted. Treatment of rats with 5,7-dihydroxytryptamine and DSP4 produced selective depletions of serotonin (79–95%) and NE (69–85%), respectively, in cortical and hippocampal brain regions. The degree of cortical NE-stimulated PI breakdown in the lesioned animals was not significantly different from that in the control animals, suggesting that under the conditions used, serotonin and NE depletion do not lead to a changed sensitivity of alpha1-adrenoceptors coupled to PI breakdown in the rat cortex.

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.

Similar content being viewed by others

References

  • Archer T, Jonsson G, Minor GB, Post C (1986) Noradrenergic-serotonergic interactions and nociception in the rat. Eur J Pharmacol 120: 295–308

    Google Scholar 

  • Berridge MJ, Downes CP, Hanley MR (1982) Lithium amplifies agonist-dependent phosphatidylinositol responses in brain and salivary glands. Biochem J 206: 587–595

    Google Scholar 

  • Brown E, Kendall DA, Nahorski SR (1984) Inositol phospholipid hydrolysis in rat cerebral cortical slices: I. Receptor characterization. J Neurochem 42: 1379–1387

    Google Scholar 

  • Brunello N, Barbacchia ML, Chuang D-M, Costa E (1982) Down-regulation of β-adrenergic receptors following repeated injections of desmethylimipramine: permissive role of serotonergic axons. Neuropharmacology 21: 1145–1149

    Google Scholar 

  • Consolo S, Wang J-X, Forloni GL, Mocchetti I, Racagni G, Ladinsky H (1985) Studies on the up regulation of alpha-adrenoceptors on rat hippocampal perikarya by chemical lesion of the median Raphe nucleus. Life Sci 37: 449–460

    Google Scholar 

  • Dooley DJ, Bittiger H, Hauser KL, Bischoff SF, Waldmeier PC (1983) Alteration of central alpha2-and beta-adrenergic receptors in the rat after DSP-4, a selective noradrenergic neurotoxin. Neuroscience 9: 889–898

    Google Scholar 

  • Durkin TA, Caliguri EJ, Mefford IM, Lake DM, McDonald IA, Sundström E, Jonsson G (1985) Determination of catecholamines in tissue and body fluids using microbore and high pressure liquid chromatography with amperometric detection. Life Sci 37: 1803–1810

    Google Scholar 

  • Fowler CJ (1984) Receptor binding studies: yet more cause for caution. Trends Pharmacol Sci 5: 498–499

    Google Scholar 

  • Fowler CJ, Fagervall I, Minor BG, Ross SB (1986a) α1-adrenoceptor function in the rat hippocampus as assessed by noradrenaline-stimulated inositol phospholipid breakdown after destruction of noradrenergic neurons by neonatal 6-hydroxydopamine treatment. J Pharm Pharmacol 38: 385–388

    Google Scholar 

  • Fowler CJ, O'Carroll A-M, Court JA, Candy JM (1986b) Stimulation by noradrenaline of inositol phospholipid breakdown in the rat hippocampus: effect of the ambient potassium concentration. J Pharm Pharmacol 38: 201–208

    Google Scholar 

  • Fowler CJ, Magnusson O, Mohammed AK, Danysz W, Archer T (1986c) The effect of selective noradrenergic lesions upon the stimulation by noradrenaline of inositol phospholipid breakdown in rat hippocampal miniprisms. Eur J Pharmacol 123: 401–4407

    Google Scholar 

  • Fowler CJ, Court JA, Tiger G, Björklund P-E, Candy JM (1987) Stimulation of inositol phospholipid breakdown in rat cortical and hippocampal miniprisms by noradrenaline, 5-hydroxytryptamine and carbachol: some methodological aspects. Pharmacol Toxicol 60: 274–279

    Google Scholar 

  • Godfrey PP, Grahame-Smith DG, Heal DJ, McClue SJ, Young MM (1987) 5-HT stimulated PI turnover does not reflect altered 5-HT2 function after antidepressants or neurochemical lesioning. Br J Pharmacol 90: 76P

  • Hallman H, Jonsson G (1984) Pharmacological modifications of the neurotoxic action of the noradrenaline neurotoxin DSP4 on central noradrenaline neurons. Eur J Pharmacol 103: 269–278

    Google Scholar 

  • Hallman H, Sundström E, Jonsson G (1984) Effects of the noradrenaline neurotoxin DSP4 on monoamine neurons and their transmitter turnover in rat CNS. J Neural Transm 60: 89–102

    Google Scholar 

  • Janowsky A, Labarca R, Paul SM (1984) Noradrenergic denervation increases α1-adreno-ceptor-mediated inositolphosphate accumulation in the hippocampus. Eur J Pharmacol 102: 193–194

    Google Scholar 

  • Jones SB, Bylund DB (1986) Ascorbic acid inhibition of alpha-adrenergic receptor binding. Biochem Pharmacol 35: 595–599

    Google Scholar 

  • Jonsson G, Hallman H, Sundström E (1982) Effects of the noradrenaline neurotoxin DSP4 on the postnatal development of central noradrenaline neurons in the rat. Neuroscience 7: 2895–2907

    Google Scholar 

  • Kendall DA, Brown E, Nahorski SR (1985) α1-Adrenoceptor-mediated inositol phospholipid hydrolysis in rat cerebral cortex: relationship between receptor occupancy and response and effects of denervation. Eur J Pharmacol 114: 41–52

    Google Scholar 

  • Logue MP, Growdon JH, Coviella ILG, Wurtman RJ (1985) Differential effects of DSP-4 administration on regional brain norepinephrine turnover in rats. Life Sci 37: 403–409

    Google Scholar 

  • Minneman KP, Johnson RD (1984) Characterization of alpha-1 adrenergic receptors linked to [3H]inositol metabolism in rat cerebral cortex. J Pharmacol Exp Ther 230: 317–323

    Google Scholar 

  • Morrow AL, Norman AB, Battaglia G, Loy R, Creese I (1985) Up-regulation of serotonergic binding sites labeled by [3H]WB4101 following fimbrial transection and 5,7-dihydroxytryptamine-induced lesions. Life Sci 37: 1913–1922

    Google Scholar 

  • Nimgaonkar VL, Goddwin GM, Davies CL, Green AR (1985) Down-regulation of β-adrenoceptors in rat cortex by repeated administration of desipramine, electroconvulsive shock and clenbuterol requires 5-HT neurones but not 5-HT. Neuropharmacology 24: 279–283

    Google Scholar 

  • Norman AB, Battaglia G, Morrow AL, Creese I (1985) [3H]WB4101 labels S1 serotonin receptors in rat cerebral cortex. Eur J Pharmacol 106: 461–462

    Google Scholar 

  • Rappaport A, Sturtz F, Guicheney P (1985) Regulation of central α-adrenoceptors by serotoninergic denervation. Brain Res 344: 158–161

    Google Scholar 

  • Schoepp DD, Knepper SM, Rutledge CO (1984) Norepinephrine stimulation of phosphoinositide hydrolysis in rat cerebral cortex is associated with the alpha1-adrenoceptor. J Neurochem 43: 1758–1761

    Google Scholar 

  • Stockmeier CA, Martino AM, Kellar KJ (1985) A strong influence of serotonin axons on β-adrenergic receptors in rat brain. Science 230: 323–325

    Google Scholar 

  • Watson SP, Downes CP (1983) Substance P induced hydrolysis of inositol phospholipids in guinea-pig ileum and rat hypothalamus. Eur J Pharmacol 93: 245–253

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Fowler, C.J., Thorell, G., Sundström, E. et al. Norepinephrine-stimulated inositol phospholipid breakdown in the rat cerebral cortex following serotoninergic lesion. J. Neural Transmission 73, 205–215 (1988). https://doi.org/10.1007/BF01250137

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01250137

Keywords

Navigation