EFFECTS OF DOPAMINE RECEPTOR AGONISTS ON THE RELEASE AND CONTENTS OF ACETYLCHOLINE AND CHOLINE IN SUPERFUSED BRAIN SLICES FROM RAT STRIATUM
Öz
AİM: The aim of the study was to determine effects of dopamine receptor agonist on acetylcholine and choline release from rat brain striatal slices and tissue levels of acetylcholine, choline and phospholipid. Methods: Spraque-Dawley rats 250-350 g were decapitated and their brains were rapidly removed, the striata were dissected and sliced with 0.3 mm thickness. Slices were perfused with heated 37 °C and oxygenated 95% O2 + 5% CO2 Krebs medium 0.6 ml/min under basal and stimulated either with high K+ or electrically conditions with presence of various concentrations of dopamine receptor agonists. Acetylcholine and choline contents of the perfusates, and tissue levels of acetylcholine, choline, protein, DNA and phospholipids were assayed Results: Dopamine receptor agonists [apomorphine 1-100 μM , dopamine 1-100 μM , bromocriptine 0.1-10 μM , piripedil 1-100 μM , quinpirole 1 and 10 μM and SKF 38393 1 and 10 μM failed to alter amounts of acetylcholine and choline released into the perfusate from striatal slices under basal conditions. While selective D1 receptor agonist SKF 38393 increased acetylcholine release at 100 μM. When the slices depolarized by high K+ 50 μM or stimulated electrically 15 Hz, 1 ms, 80 mA release of acetylcholine increased by 7-20 folds. Apomorphine, piribedil or quinpirole, but not dopamine, bromocriptine or SKF 38393, decreased acetylcholine release, by concentration dependent manner, during K+ depolarization and electrical stimulation. Dopamine receptors agonists failed to alter choline release, tissue levels of acetylcholine, choline and phospholipids at used concentrations. Conclusion: These data show that dopamine receptor agonists have no effects on acetylcholine and choline release from the striatal slices under basal perfusion conditions, while some of agonists i.e., apomorphine, piribedil and quinpirole suppressed acetylcholine release from the stimulated slices. Dopamine receptor agonists have no effect on choline release and tissue contents of acetylcholine, choline and phospholipids
Anahtar Kelimeler
Kaynakça
- Anda M, Iwara M, Takahama K, Nagata Y. Effects of extracellular choline concentration and K4 depolarization on choline kinase and choline acetyltransferase activities in superior cervical sympathetic ganglia excised from rats. J Neurochem 1987; 48: 1448-1453.
- Farber SA, Savci V, Slack BE, Wurtman RJ. Choline’s phosphorylation in rat striatal slices is regulated by the activity of cholinergic neurons. Brain Res 1996; 723: 90-99.
- 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.
- Blusztajn JK, Holbrook PG, Lakher M, Liscovitch M, Maire JC, Mauron C, Richardson UI, Tacconi M, Wurtman RJ. “Autocannibalism” of membrane choline-phospholipids: physiology and pathology. Psychopahramacological Bull 1986; 22: 781-786.
- Wurtman RJ. Choline metabolism as a basis for the selective vulnerability of cholinergic neurons. TINS 1992; 15: 117-122.
- Tan CO, Bullock D. A dopamine-acetylcholine cascade: stimulating learned and lesion-induced behaviou of striatal cholinergic interneurons. J Neurophysiol 2008; 100: 2409-2421.
- 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.
- Exley R, Cragg SJ. Presynaptic nicotinic receptors: a dynamic and diverse cholinergic fitler of striatal dopamine neurotransmission. Br J Pharmacol 2008; 153: 5283-5297.
- 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.
- Stoof JC, Kebabian JW. Independent in vitro regulation by the D-2 dopamine receptor of dopamine-stimulated efflux 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.
- Gorell JM, Czarnecki B, Hubbell S. Functional antagonism of D1 and D2 dopaminergic mechanism affecting striatal acetylcholine release. Life Sci 1986; 38: 2247-2254.
- Drukarch B, Schepens E, Schoffelmeer 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.
- Wang H-Y, Zhou L-W, Friedman E, Weiss B. Differential regulation of release of acetylcholine in the striatum in mice following continuos exposure to selective D1 and D2 dopaminergic agonists. Neuropharmacol 1993; 32: 85-91.
- 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. Proteinmeasurement with the folin phenol reagent. J Biol Chem 1951; 193: 265-275.
- Savanborg A, Svennerholm L. Plasma total lipids, cholesterol, triglycerides, phospholipids and free fatty acids in a healty Scandinavian population. Acta Med Scand 1961; 169: 43-49.
Dopamin Reseptör Agonisti Maddelerin Sıçan Beyni Striatal Dilimlerinde Kolin ve Asetilkolin Salıverilmesine, Doku Kolin, Asetilkolin ve Fosfolipid Düzeylerine Etkisi
Öz
Amaç: Bu çalışmanın amacı dopamin reseptör agonisti maddelerin sıçan striatal beyin dilimlerinden asetilkolin ve kolin salıverilmesine ve doku asetilkolin, kolin ve fosfolipid düzeylerine etkilerini incelemektir. Yöntemler: Başları kesilerek öldürülen 250-350 g ağırlığında erkek SpraqueDawley türü sıçanlardan beyinler hızla çıkarıldı ve soğutulmuş fizyolojik solüsyon içinde striatal bölge çıkarıldı ve 0,3 mm kalınlığında dilimlendi. Dilimler oksijene edilen ve ısıtılan fizyolojik Krebs solüsyonu ile bazal koşullarda, elektrikle ya da yüksek potasyumla uyarılarak perfüze 0,6 ml/dakika edildiler. Dopamin agonistleri perfüzyon ortamına değişik konsantrasyonlarda eklendi ve toplanan perfüzatlarda asetilkolin ve kolin ölçüldü. Deneyin sonunda ve dopamin agonistleri eklenmeden önce dilimlerden örnekler alınarak doku asetilkolin, kolin, protein, DNA ve fosfolipid düzeyleri ölçüldü. Bulgular: Perfüzyon ortamına değişik konsantrasyonlarda eklenen dopamin reseptör agonistleri [dopamin 1-100 μM , apomorfin 1-100 μM , bromokriptin 0,1-10 μM , piripedil 1-100 μM , kuinpirol 1-10 μM ve SKF 38393 1 ve 10 μM bazal koşullarda salıverilen asetilkolin ve kolin miktarını değiştirmedi. Secici D1 agonisti olan SKF 38393 ise, ortamda 100 μM düzeyde bulunduğunda asetilkolin salıverilmesini arttırdı. Elektrikle ya da yüksek potasyumla 50 μM uyarılma durumunda dilimlerden asetilkolin salıverilmesi 7-20 kat kadar arttı. Ortamda apomorfin, piripedil ya da kuinpirol bulunması uyarılmanın yol açtığı asetilkolin salıverilmesini konsantrasyona bağlı olarak azalttı. Diğer agonistler dopamin, bromokriptin ve SKF 38393 ise, uyarılmanın neden olduğu asetilkolin salıverilmesine etkisizdi. Dopamin reseptör agonistleri dilimlerden kolin çıkışını, doku asetilkolin, kolin ve fosfolipid düzeylerini etkilemedi. Sonuçlar: Bu bulgular dopamin reseptör agonistlerinin bazal koşullarda striatal dilimlerden asetilkolin ve kolin çıkışına etkisizken, uyarılan dilimlerden asetilkolin çıkışının bazı agonistlerce apomorfin, piripedil ve kuinpirol gibi baskılandığı göstermektedir. Dopamin reseptör agonistlerinin striatal dilimlerde kolin çıkışını, doku asetilkolin, kolin ve fosfolipid düzeylerine etkisi yoktur.
Anahtar Kelimeler
Kaynakça
- Anda M, Iwara M, Takahama K, Nagata Y. Effects of extracellular choline concentration and K4 depolarization on choline kinase and choline acetyltransferase activities in superior cervical sympathetic ganglia excised from rats. J Neurochem 1987; 48: 1448-1453.
- Farber SA, Savci V, Slack BE, Wurtman RJ. Choline’s phosphorylation in rat striatal slices is regulated by the activity of cholinergic neurons. Brain Res 1996; 723: 90-99.
- 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.
- Blusztajn JK, Holbrook PG, Lakher M, Liscovitch M, Maire JC, Mauron C, Richardson UI, Tacconi M, Wurtman RJ. “Autocannibalism” of membrane choline-phospholipids: physiology and pathology. Psychopahramacological Bull 1986; 22: 781-786.
- Wurtman RJ. Choline metabolism as a basis for the selective vulnerability of cholinergic neurons. TINS 1992; 15: 117-122.
- Tan CO, Bullock D. A dopamine-acetylcholine cascade: stimulating learned and lesion-induced behaviou of striatal cholinergic interneurons. J Neurophysiol 2008; 100: 2409-2421.
- 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.
- Exley R, Cragg SJ. Presynaptic nicotinic receptors: a dynamic and diverse cholinergic fitler of striatal dopamine neurotransmission. Br J Pharmacol 2008; 153: 5283-5297.
- 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.
- Stoof JC, Kebabian JW. Independent in vitro regulation by the D-2 dopamine receptor of dopamine-stimulated efflux 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.
- Gorell JM, Czarnecki B, Hubbell S. Functional antagonism of D1 and D2 dopaminergic mechanism affecting striatal acetylcholine release. Life Sci 1986; 38: 2247-2254.
- Drukarch B, Schepens E, Schoffelmeer 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.
- Wang H-Y, Zhou L-W, Friedman E, Weiss B. Differential regulation of release of acetylcholine in the striatum in mice following continuos exposure to selective D1 and D2 dopaminergic agonists. Neuropharmacol 1993; 32: 85-91.
- 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. Proteinmeasurement with the folin phenol reagent. J Biol Chem 1951; 193: 265-275.
- Savanborg A, Svennerholm L. Plasma total lipids, cholesterol, triglycerides, phospholipids and free fatty acids in a healty Scandinavian population. Acta Med Scand 1961; 169: 43-49.
Ayrıntılar
| Birincil Dil | Türkçe |
|---|---|
| Bölüm | Correction |
| Yazarlar | |
| Yayımlanma Tarihi | 1 Aralık 2010 |
| Yayımlandığı Sayı | Yıl 2010Sayı: 4 |