EFFECTS OF DOPAMINE RECEPTOR ANTAGONISTS ON ACETYLCHOLINE AND CHOLINE RELEASE FROM RAT BRAIN STRIATAL SLICES
Abstract
Objective: The aim of the study was to determine the effects of dopamine receptor antagonists on acetylcholine and choline metabolism in rat brain striatal slices. Methods: Striatal slices from rat brain were perfused with physiological medium under basal and stimulated conditions in the presence of various concentrations of dopamine receptor antagonists. Acetylcholine and choline contents of the perfusate and tissue were assayed radioenzymatically. Results: Under resting conditions the rate of acetylcholine and choline release into the pefusate were 49±5 pmol/mg protein/10 min and 321±14 pmol/mg protein/10 min, respectively. Presence of dopamine receptor antagonists [Flufenazin 0,1-100 μM , haloperidol 1-10 μM , thioridazine 1-10 μM , sulpride 1-100 μM and eticlopride 1-10 μM ] in the perfusion medium failed to alter the basal rate of acetylcholine and choline release. When the slices were stimulated by high K+ 50 μM or electrically 15 Hz, 1 ms ve 80 mA , the release of acetylcholine increased to 938±108 pmol/ mg protein/10 min or 398±22 pmol/mg protein/10 min, respectively. Sulpride 100 μM and eticlopride 10 μM , but not flufenazin 0,1-100 μM , haloperidol 1-10 μM or thioridazine 1-10 μM , decreased acetylcholine release by about 50%, during electrical or high K+ stimulation. Flufenazine 10 μM attenuated the decrease in acetylcholine release induced by piripedil 100 μM , an agonist of dopamine receptors, during K+ depolarization. Sulpride 100 μM or eticlopride 10 μM failed to block the effect of piripedil on acetylcholine release during electrical or high K+ stimulation, contrarily they showed tendency to enhance it. Chemical destruction of dopamine neurons by 6-hydroxydopamine decreased dopamine release but failed to alter acetylcholine and choline release from the striatal slices either at rest or during stimulation. Conclusion: These data show that some dopamine receptor antagonists e.g., sulpride and eticloprid , but not others e.g., flufenazine, haloperidol and thioridazine , decrease acetylcholine release from stimulated striatal slices without altering choline release, and tissue contents of acetylcholine and choline
References
- Kawaguchi Y, Wilson CJ, Augood SJ, Emson PC. Striatal interneurones: chemical, physiological and morphological characterization. TINS 1995; 18: 527-535.
- Catabresi P, Centonze D, Gubelleni P, Pisani A, Bernardi G. Acetylcholine-mediated modulation of striatal function. Trends Neurosci 2000; 23: 120-126.
- Pollack AE. Anatomy, physiology, and pharmacology of the basal ganglia. Neurol Clin 2001; 19: 523-534.
- Afi fi AK. The basal ganglia: a neural network with more than motor function. Semin Pediatr Neurol 2003; 10: 1-10.
- Pisani A, Bonsi P, Centonze D, Gubellini P, Bernardi G, Calabresi P. Targeting striatal cholinergic interneurons in Parkinson’s disease: focus on metabotropic glutamate receptors. Neuropahrmacology 2003; 45: 45-56.
- Calabresi P, Di Filippo M. ACh/dopamine crosstalk in motor control and reward: a crucial role for alpha 6-contaning nicotinic receptors? Neuron 2008; 60: 4-7.
- Tan CO, Bullock D. A dopamine-acetylcholine cascade: stimulating learned and lesion-induced behaviour of striatal cholinergic interneurons. J Neurophysiol 2008; 100: 2409-2421.
- Salin P, Lopez IP, Kachidian P, Barroso-Chinea P, Rico AJ, Gomez-Bautista V, Coulon P, Kerkerian-Le GL, Lanciego JL. Changes to interneuron-direven striatal microcircuits in a rat model of Parkinson’s disease. Nurobiol Dis 2009; 34: 545-552.
- Cebrian C, Prensa L. Basal ganglia and thalamic input from neurons located within the ventral tier cell cluster region of the substantia nigra pars compacta in the rat. J Comp Neurol 2010; 518 : 1283-1300.
- Lester DB, Rogers TD, Blaha CD. Acetylcholine-dopamine interactions in the pathophysiology and treatment of CNS disorders. CNS Neurosci Ther 2010; 16:137-162.
- Stoof JC, Kebabian JW. Independent in vitro regulation by the D-2 dopamine receptor of dopamine-stimulated effl ux of cyclic AMP and K+- stimulated release of acetylcholine from rat striatum. Brain Res 1982; 250: 263-270.
- Gorell JM, Czarnecki B. Pharmacological evidence for direct dopaminergic regulation of striatal acetylcholine release. Life Sci 1986; 38: 2239-2246.
- Damsma G, de Boer P, Westerink BHC, Fibiger HC. Dopaminergic regulation of striatal cholinergic interneurons: an in vivo microdialysis study. Naunyn-Schmiedeberg’s Arch Pharmacol 1990; 342: 523-527.
- Drukarch B, Schepens E, Schoff elmeer AN, Stoof JC. Stimulation of D-2 dopamine receptors decreases the evoked in vitro release of [3H]acetylcholine from rat neostriatum: role of K+ and Ca2+. J Neurochem 1989; 52: 1680-1685.
- Ikarashi Y, Tkahashi A, Ishimaru H, Arai T, Maruyama Y. Regulation of dopamine D1 and D2 receptors on striatal acetylcholine release in rats. Brain res Bull 1997; 43: 107-115.
- Pisani A, Bonsi P, Centonze D, Calabresi P, Bernardi G. Activation of D2-like dopamine receptors reduces synaptic inputs to striatal cholinergic interneurons. J Neurosci 2000; 20: RC69 (1-6).
- Ding Y-S, Logan J, Bermel R, Garza V, Rice O, Fowler JS, Volkow ND. Dopamine receptor-mediated regulation of striatal cholinergic activity: Positron emission tomography studies with norchloro[18F]fl uoroepibatidine. J Neurochem 2000; 74: 1514-1521.
- Acquas E, Di Chiara G. Role of dopamine D1 receptors in the control of striatal acetylcholine release by endogenous dopamine. Neurol Sci 2001; 22: 41-42.
- Adachi YU, Watanabe K, Higushi H, Satoh T, Zsilla G. Halothane enhances acetylcholine release by decreasing dopaminergic activity in rat striatal slices. Neurochem Int 2002; 40: 189-193.
- Rakovska A, Raichev JD, Ang R, Balla A, Aspromonte J, Vizi S. Physiological release of striatal acetylcholine (in vivo): eff ect of somatostatin on dopaminergic-cholinergic interaction. Brain Re Bull 2003; 61: 529-536.
- Ulus IH.Dopamin reseptör agonisti maddelerin sıçan beyni stiatal dilimlerinde kolin ve asetilkolin salıverilmesine, doku kolin, asetilkolin ve fosfolipid düzeylerine etkisi. Acibadem Dergisi 2010; 3 : 145-158 .
- Ulus IH, Kiran BK. The eff ect of 6-hydroxydopamine on the tolerance development to the hyperthermic eff ect of (+)-amphetamine in rat. J Pharm Pharmac 1975; 27: 205-206.
- Ulus IH, Kiran BK, Ozkurt S. Involvement of central dopamine in the hyperthermia in rats produced by d-amphetamine. Pharmacology 1975; 13; 309-316.
- Gilberstadt ML, Russell JA. Determination of picomole quantities of acetylcholine and choline in physiological salt solutions. Anal Biochem 1984; 138: 78-85.
- Goldberg AM, McCaman RE. The determination of picomole amounts of acetylcholine in mammalian brain. J Neurochem 1973; 20: 1-8.
- Lowry OH, Rosenbrough NJ, Farr AL, Randall RJ. Protein measurement with the folin phenol reagent. J Biol Chem 1951; 193: 265-275.
- Ulus IH, Wurtman RJ, Mauron C, Blusztajn JK. Choline increases acetylcholine release and protects against the stimulation-induced decrease in phosphatide levels within membranes of rat corpus striatum. Brain Res 1989; 484: 217-227.
- Buyukuysal RL, Wurtman RJ. 4-Aminopyridine increases acetylcholine release without dimisnishing membrane phosphatidylcholine. J Neurochem 1990; 54: 1302-1309.
- Ulus IH, Buyukuysal RL, Wurtman RJ. N-Methyl-D-Aspartate increases acetylcholine release from rat striatum and cortex: Its eff ect is augmented by choline. J Pharmacol Exp Ther 1992; 261: 1122-1128.
- Ulus IH, Watkins CJ, Cansev M, Wurtman RJ. Cytidine and uridine increase striatal CDP-choline levels without decreasing acetylcholine syhthesis or release. Cell Mol Neurobiol 2006; 26: 563-577.
- Martelle JL, Nader MA. A review of the discovery, pharmacological characterization, and behavioral eff ects of the dopamine D2-like receptor antagonist eticlopride. CNS Neurosci Ther 2008; 14: 248-262.
- Wurtman RJ. Choline metabolism as a basis fort he selective vulnerability of cholinergic neurons. TINS 1992; 15: 117-122.
- MacKenzie RG, Stachowiak MK, Zigmond MJ. Dopamine inhibition of stritala acetylcholine release after 6-hydroxydopamine. Eur J Pharmacol 1989; 168: 43-52.
- Löschmann PA, De Groote C, Albrecht C, Darstein M, Deransart C, Landwehrmeyer GB, Lücking CH, Feurstein TJ. [3H]acetylcholine release in rat striatal slices is not subject to dopamine heteroreceptor supersensistivity 30 months after 6-hydroxydopamine lesion of substantia nigra. Naunyn Schmiedebergs Arch Pharmacol 2001; 363: 414-421.
- Fenu S, Acquas E, Di Chiara G. Role of striatal acetylcholine on dopamine D1 receptor agonist-induced turning behaviot in 6-hydroxydopamine lesioned rats: a microdialysis-behavioral study. Neurol Sci 2001; 22: 63-64
Sıçan Striatal Dilimlerinden Bazal ve Uyarılma Koşullarında Asetilkolin ve Kolin Salıverilmesine Dopamin Reseptör Antagonistlerinin Etkisi
Abstract
Amaç: Bu çalışmanın amacı dopamin reseptör antagonisti maddelerin sıçan striatal beyin dilimlerinden asetilkolin ve kolin metabolizmasına etkilerini incelemekti. Yöntemler: Sıçan beyninden striatal bölgeden hazırlanmış dilimler değişik düzeylerde dopamin reseptör antagonisti içeren fizyolojik sıvı solüsyonla bazal ve uyarılma koşullarında perfüze edildi. Perfüzata salıverilen ve dokuda bulunan asetilkolin ve kolin radioenzimatik yöntemle ölçüldü. Bulgular: Striatal dilimlerden bazal ve uyarılma koşullarında perfüzata asetilkolin ve kolin salıverilme hızları, sırayla, 49±5 pmol/mg protein/10 dakika ve 321±14 pmol/mg protein/10 dakika oldu. Ortamda dopamin reseptör antagonistlerin [flufenazin 0,1-100 μM , haloperidol 1-10 μM , thioridazin 1-10 μM , sulpirid 1-10 μM ve etiklopirid 1-10 μM ] bulunması perfüzata asetilkolin ve kolin’in bazal salıverilme hızını etkilemedi. Striatal dilimler yüksek K+ 50 μM ya da elektrikle 15 Hz, 1 ms ve 80 mA uyarıldığında asetikolin salıverilme hızı artarak, sırayla, 938±108 pmol/mg protein/10 dakika ya da 398±22 pmol/mg protein 10 dakika’ya çıktı. Sulpirid 100 μM ve etiklopirid 10 μM yüksek poatsyumla ya da elektrikle uyarılma sırasındaki asetilkolin salıverilmesini %50 kadar baskılarken, flufenazin 0,1-100 μM haloperidol 1-10 μM , thioridazin 1-10 μM etkisiz oldu. Flufenazin 10 μM dopamin reseptör agonisti piripedil’in yüksek potasyumla uyarılma sırasında asetilkolin salıverilmesinde neden olduğu baskılanmayı önledi. Sulpirid 100 μM ve etiklopirid 10 μM piripedil’in yüksek K+ uyarılma sırasında asetilkolin salıverilmesine olan etkisini bloke edemediler ve arttırıcı yönde etki gösterdiler. Dopamin nöronlarının 6-hidroksidopamin tarafında kimyasal tahribi striatal dilimlerden bazal ve uyarılma koşullarında dopamin salıverilmesini azalttı, fakat asetilkolin ve kolin salıverilmesini etkilemedi. Sonuçlar: Bu bulgular bazı dopamin reseptör antagonistlerinin sulpirid ve etiklopirid gibi uyarılan strital dilimlerden kolin salıverilmesini etkilemeden asetilkolin salıverilmesini baskıladıklarını, diğerlerinin flufenazin, thioridazin, haloperidol gibi ise böyle bir etkisi olmadığını göstermektedir.
References
- Kawaguchi Y, Wilson CJ, Augood SJ, Emson PC. Striatal interneurones: chemical, physiological and morphological characterization. TINS 1995; 18: 527-535.
- Catabresi P, Centonze D, Gubelleni P, Pisani A, Bernardi G. Acetylcholine-mediated modulation of striatal function. Trends Neurosci 2000; 23: 120-126.
- Pollack AE. Anatomy, physiology, and pharmacology of the basal ganglia. Neurol Clin 2001; 19: 523-534.
- Afi fi AK. The basal ganglia: a neural network with more than motor function. Semin Pediatr Neurol 2003; 10: 1-10.
- Pisani A, Bonsi P, Centonze D, Gubellini P, Bernardi G, Calabresi P. Targeting striatal cholinergic interneurons in Parkinson’s disease: focus on metabotropic glutamate receptors. Neuropahrmacology 2003; 45: 45-56.
- Calabresi P, Di Filippo M. ACh/dopamine crosstalk in motor control and reward: a crucial role for alpha 6-contaning nicotinic receptors? Neuron 2008; 60: 4-7.
- Tan CO, Bullock D. A dopamine-acetylcholine cascade: stimulating learned and lesion-induced behaviour of striatal cholinergic interneurons. J Neurophysiol 2008; 100: 2409-2421.
- Salin P, Lopez IP, Kachidian P, Barroso-Chinea P, Rico AJ, Gomez-Bautista V, Coulon P, Kerkerian-Le GL, Lanciego JL. Changes to interneuron-direven striatal microcircuits in a rat model of Parkinson’s disease. Nurobiol Dis 2009; 34: 545-552.
- Cebrian C, Prensa L. Basal ganglia and thalamic input from neurons located within the ventral tier cell cluster region of the substantia nigra pars compacta in the rat. J Comp Neurol 2010; 518 : 1283-1300.
- Lester DB, Rogers TD, Blaha CD. Acetylcholine-dopamine interactions in the pathophysiology and treatment of CNS disorders. CNS Neurosci Ther 2010; 16:137-162.
- Stoof JC, Kebabian JW. Independent in vitro regulation by the D-2 dopamine receptor of dopamine-stimulated effl ux of cyclic AMP and K+- stimulated release of acetylcholine from rat striatum. Brain Res 1982; 250: 263-270.
- Gorell JM, Czarnecki B. Pharmacological evidence for direct dopaminergic regulation of striatal acetylcholine release. Life Sci 1986; 38: 2239-2246.
- Damsma G, de Boer P, Westerink BHC, Fibiger HC. Dopaminergic regulation of striatal cholinergic interneurons: an in vivo microdialysis study. Naunyn-Schmiedeberg’s Arch Pharmacol 1990; 342: 523-527.
- Drukarch B, Schepens E, Schoff elmeer AN, Stoof JC. Stimulation of D-2 dopamine receptors decreases the evoked in vitro release of [3H]acetylcholine from rat neostriatum: role of K+ and Ca2+. J Neurochem 1989; 52: 1680-1685.
- Ikarashi Y, Tkahashi A, Ishimaru H, Arai T, Maruyama Y. Regulation of dopamine D1 and D2 receptors on striatal acetylcholine release in rats. Brain res Bull 1997; 43: 107-115.
- Pisani A, Bonsi P, Centonze D, Calabresi P, Bernardi G. Activation of D2-like dopamine receptors reduces synaptic inputs to striatal cholinergic interneurons. J Neurosci 2000; 20: RC69 (1-6).
- Ding Y-S, Logan J, Bermel R, Garza V, Rice O, Fowler JS, Volkow ND. Dopamine receptor-mediated regulation of striatal cholinergic activity: Positron emission tomography studies with norchloro[18F]fl uoroepibatidine. J Neurochem 2000; 74: 1514-1521.
- Acquas E, Di Chiara G. Role of dopamine D1 receptors in the control of striatal acetylcholine release by endogenous dopamine. Neurol Sci 2001; 22: 41-42.
- Adachi YU, Watanabe K, Higushi H, Satoh T, Zsilla G. Halothane enhances acetylcholine release by decreasing dopaminergic activity in rat striatal slices. Neurochem Int 2002; 40: 189-193.
- Rakovska A, Raichev JD, Ang R, Balla A, Aspromonte J, Vizi S. Physiological release of striatal acetylcholine (in vivo): eff ect of somatostatin on dopaminergic-cholinergic interaction. Brain Re Bull 2003; 61: 529-536.
- Ulus IH.Dopamin reseptör agonisti maddelerin sıçan beyni stiatal dilimlerinde kolin ve asetilkolin salıverilmesine, doku kolin, asetilkolin ve fosfolipid düzeylerine etkisi. Acibadem Dergisi 2010; 3 : 145-158 .
- Ulus IH, Kiran BK. The eff ect of 6-hydroxydopamine on the tolerance development to the hyperthermic eff ect of (+)-amphetamine in rat. J Pharm Pharmac 1975; 27: 205-206.
- Ulus IH, Kiran BK, Ozkurt S. Involvement of central dopamine in the hyperthermia in rats produced by d-amphetamine. Pharmacology 1975; 13; 309-316.
- Gilberstadt ML, Russell JA. Determination of picomole quantities of acetylcholine and choline in physiological salt solutions. Anal Biochem 1984; 138: 78-85.
- Goldberg AM, McCaman RE. The determination of picomole amounts of acetylcholine in mammalian brain. J Neurochem 1973; 20: 1-8.
- Lowry OH, Rosenbrough NJ, Farr AL, Randall RJ. Protein measurement with the folin phenol reagent. J Biol Chem 1951; 193: 265-275.
- Ulus IH, Wurtman RJ, Mauron C, Blusztajn JK. Choline increases acetylcholine release and protects against the stimulation-induced decrease in phosphatide levels within membranes of rat corpus striatum. Brain Res 1989; 484: 217-227.
- Buyukuysal RL, Wurtman RJ. 4-Aminopyridine increases acetylcholine release without dimisnishing membrane phosphatidylcholine. J Neurochem 1990; 54: 1302-1309.
- Ulus IH, Buyukuysal RL, Wurtman RJ. N-Methyl-D-Aspartate increases acetylcholine release from rat striatum and cortex: Its eff ect is augmented by choline. J Pharmacol Exp Ther 1992; 261: 1122-1128.
- Ulus IH, Watkins CJ, Cansev M, Wurtman RJ. Cytidine and uridine increase striatal CDP-choline levels without decreasing acetylcholine syhthesis or release. Cell Mol Neurobiol 2006; 26: 563-577.
- Martelle JL, Nader MA. A review of the discovery, pharmacological characterization, and behavioral eff ects of the dopamine D2-like receptor antagonist eticlopride. CNS Neurosci Ther 2008; 14: 248-262.
- Wurtman RJ. Choline metabolism as a basis fort he selective vulnerability of cholinergic neurons. TINS 1992; 15: 117-122.
- MacKenzie RG, Stachowiak MK, Zigmond MJ. Dopamine inhibition of stritala acetylcholine release after 6-hydroxydopamine. Eur J Pharmacol 1989; 168: 43-52.
- Löschmann PA, De Groote C, Albrecht C, Darstein M, Deransart C, Landwehrmeyer GB, Lücking CH, Feurstein TJ. [3H]acetylcholine release in rat striatal slices is not subject to dopamine heteroreceptor supersensistivity 30 months after 6-hydroxydopamine lesion of substantia nigra. Naunyn Schmiedebergs Arch Pharmacol 2001; 363: 414-421.
- Fenu S, Acquas E, Di Chiara G. Role of striatal acetylcholine on dopamine D1 receptor agonist-induced turning behaviot in 6-hydroxydopamine lesioned rats: a microdialysis-behavioral study. Neurol Sci 2001; 22: 63-64
Details
| Primary Language | Turkish |
|---|---|
| Journal Section | Research Article |
| Authors | |
| Publication Date | March 1, 2011 |
| Published in Issue | Year 2011Issue: 1 |