Sıçan Striatal Dilimlerinden Bazal ve Uyarılma Koşullarında Asetilkolin ve Kolin Salıverilmesine Dopamin Reseptör Antagonistlerinin Etkisi

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.

EFFECTS OF DOPAMINE RECEPTOR ANTAGONISTS ON ACETYLCHOLINE AND CHOLINE RELEASE FROM RAT BRAIN STRIATAL SLICES

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

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