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Striatal dopaminergic D1 and D2 receptors after intracerebroventricular application of alloxan and streptozocin in rat

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Summary

Intracerebroventricular application of low, nondiabetogenic doses (500 μg kg−1) of alloxan and streptozocin is followed by alterations of the dopaminergic system in rat striatum. In this brain region the dopamine content significantly increased, while the density of dopaminergic D1 receptors significantly decreased seven days after the intracerebroventricular application of betacytotoxics, as compared with the control group. The density of dopaminergic D2 receptors in striatum remained unchanged. Dopaminergic D1 and D2 receptors operate through signalling mechanism of G proteins, but no changes of Gs and Gi proteins content have been found in rat striatum after the intracerebroventricular application of betacytotoxics. As intracerebroventricular, nondiabetogenic administration of betacytotoxics produces changes of the striatal dopamine content and D1 receptor density similar to that produced by peripheral, diabetogenic administration of these drugs, the effect might be related not solely to pancreatic beta cells damage, but to alterations of the brain insulin system, as well.

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References

  • Abbracchio MP, Di Luca M, Di Giulio AM, Cattabeni F, Tenconi B, Goria A (1989) Dennervation and hyperinnervation in the nervous system of diabetic animal. III. Functional alterations of G proteins in diabetic encephalopathy. J Neurosci Res 24: 517–523

    Google Scholar 

  • Baskin DG, Figlewicz DP, Woods SC, Porte D, Dorsa DM (1986) Insulin in the brain. Ann Rev Physiol 49: 335–347

    Google Scholar 

  • Ding A, Nitsch R, Hoyer S (1992) Changes in brain monoaminergic neurotransmitter concentrations in rat after intracerebroventricular injection of streptozocin. J Cereb Blood Flow Metab 12: 103–109

    Google Scholar 

  • Finco C, Abbracchio MP, Malosio ML, Cattabeni F, Di Giulio AM, Paternieri B, Mantegazza P, Gorio A (1992) Diabetes-induced alterations of central nervous system G proteins. Mol Chem Neuropathol 17: 259–272

    Google Scholar 

  • Gawler D, Milligan G, Spiegel AM, Unson CG, Houslay MD (1987) Abbolition of the expression of inhibitory guanine nucleotide regulatory protein Gi activity in diabetes. Nature 327: 229–232

    Google Scholar 

  • Goldsmith P, Gierschik P, Milligan G, Unson CG, Vinitsky R, Maleh HL, Spiegel A (1987) Antibodies directed against synthetic peptides distinguish between GTP-binding proteins in neutrophil and brain. J Biol Chem 262: 14683–14688

    Google Scholar 

  • Hadjiconstantinou M, Qu ZX, Moroi-Fetters SE, Neff N (1988) Apparent loss of Gi protein activity in the diabetic retina. Eur J Pharmacol 149: 193–194

    Google Scholar 

  • Kono T, Takada M (1994) Dopamine depletion in nigrostriatal neurons in the genetically diabetic rat. Brain Res 634: 155–158

    Google Scholar 

  • Lacković Z, Šalković M (1989) Streptozotocin and alloxan produce alterations in rat brain monoamines independently of pancreatic beta cells destruction. Life Sci 46: 49–54

    Google Scholar 

  • Lacković Z, Šalković M, Kuci Z, Relja M (1990) Effect of long-lasting diabetes mellitus on rat and human brain monoamines. J Neurochem 54: 143–147

    Google Scholar 

  • Livingstone C, McLellan AR, McGregor MA, Wilson A, Connell JMC, Small M, Milligan G, Paterson KR, Houslay MD (1991) Altered G-protein expression and adenylate cyclase activity in platelets of noninsulin-dependent diabetic (NIDDM) male subjects. Biochem Biophys Acta 1096: 127–133

    Google Scholar 

  • Lozovsky D, Sailer CF, Kopin LJ (1981) Dopamine receptor binding is increased in diabetic rats. Science 214: 1031–1033

    Google Scholar 

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

    Google Scholar 

  • McCall AL (1992) The impact of diabetes on the CNS. Diabetes 41: 557–70

    Google Scholar 

  • Milligan G (1993) Agonist regulation of cellular G protein levels and distribution: mechanisms and functional implications. TIPS 14: 413–418

    Google Scholar 

  • Neer EJ, Lok JM, Wolf LG (1984) Purification and properties of the inhibitory guanine nucleotide regulatory unit of brain adenylate cylase. J Biol Chem 259: 14222–14229

    Google Scholar 

  • Noble EP, Wurtman RJ, Axelrod J (1967) A simple and rapid method for injecting 3H- norepinephrine into the lateral ventricle of the rat brain. Life Sci 6: 281–291

    Google Scholar 

  • Palmer TM, Houslay MD (1991) Determination of G-protein levels, ADP-ribosylation by cholera and pertussis toxins and the regulation of adenylyl cyclase activity in liver plasma membranes from lean and genetically diabetic (db/db) mice. Biochem Biophys Acta 1097: 193–204

    Google Scholar 

  • Schulz DW, Wyrick SD, Mailman RB (1983) (3H)SCH 23390 has the characteristics of a dopamine receptor ligand in the central nervous sytem. Eur J Pharmacol 106: 211–212

    Google Scholar 

  • Shimomura Y, Shimizu H, Takahashi M, Sato N, Uehara Y, Suwa K, Kobayashi I, Tadokoro S, Kobayashi S (1988) Changes in ambulatory activity and dopamine turnover in streptozocin-induced diabetic rats. Endocrinology 123: 2621–2625

    Google Scholar 

  • Sibley DR, Monsma FJ (1990) Molecular biology of dopamine receptors. TIPS 13: 61–69

    Google Scholar 

  • Simonds WF, Goldsmith P, Codina J, Unson CG, Spiegel A (1989) Gi2 mediates alpha2-adrenergic inhibition of adenylyl cyclase in platelet membranes: in situ identification with Galpha C-terminal antibodies. PNAS USA 86: 7809–7813

    Google Scholar 

  • Sokoloff P, Giros B, Martres MP, Bouthenet ML, Schwartz JC (1990) Molecular cloning and characterization of a novel dopamine receptor (D3) as a target for neuroleptics. Nature 347: 146–151

    Google Scholar 

  • Sternweis PC, Robinshow JD (1984) Isolation of two proteins with high affinity for guanine nucleotides from membrane of bovine brain. J Biol Chem 259: 13806–13813

    Google Scholar 

  • Stow JL, Sabolić I, Brown D (1991) Heterogenous localisation of G protein alpha subunits in rat kidney. Am J Physiol 261: F831-F840

    Google Scholar 

  • Šalković M (1992) Diabetes mellitus and brain dopamine. Thesis, Zagreb, Croatia

    Google Scholar 

  • Šalković M, Lacković Z (1992) Brain D1 dopamine receptor in alloxan-induced diabetes. Diabetes 41: 1119–1121

    Google Scholar 

  • Trulson ME, Himmel CD (1983) Decreased brain dopamine synthesis rate and increased (3H) spiroperidol binding in streptozotocin-diabetic rats. J Neurochem 40: 1456–1459

    Google Scholar 

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Šalković, M., Sabolić, I. & Lacković, Z. Striatal dopaminergic D1 and D2 receptors after intracerebroventricular application of alloxan and streptozocin in rat. J. Neural Transmission 100, 137–145 (1995). https://doi.org/10.1007/BF01271536

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  • DOI: https://doi.org/10.1007/BF01271536

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