Elektriksel olarak uyarılan sıçan ileum kasılma yanıtları üzerine histamin H3 reseptörleri ve nitrik oksitin rolü

Çalışlmanın amacı, histamin reseptörlerinin ileum düz kas kasılmaları üzerine olan etkilerini ve bu etkiler üzerinde nitrik oksitin olası rolünü gözlemlemektir. İzole edilen sıçan ileum preparatları organ banyosuna asılarak ortama histamin agonist ve antagonistleri ilave edildi ve doku örneklerinin elektriksel alan stimülasyonuna verdikleri kasılma yanıtları incelendi. NO donörü Derivative 28'in kobaylarda H3 antagonistik etkisinin bulunması nedeniyle H3 reseptörleri ile NO aras›nda herhangi bir etkileflimin bulunup bulunmadığı incelendi. Histamin H1, H2, H3 reseptörlerinden biri bloke edildikten sonra elektriksel stimülasyona verilen kasılma yanıtlarının ne yönde değişleceğini gözlemlemek amacıyla diğer reseptörlerin biri veya her ikisi bloke edilerek kasılma yanıtlarındaki farklılıklar izlendi. Histamin reseptörlerini bloke etmek amacıyla H1 reseptör blokeri olarak pirilamin (10-6 Μ), H2 reseptör blokeri olarak famotidin (10-6 Μ) ve H3 reseptör blokeri olarak tiyoperamid (10-5 Μ) ve bunların çeşitli kombinasyonları kullanıldı. Tüm gruplarda H3 reseptör agonisti (R)-α-metilhistaminin 10-8, 10-7, 10-6 ve 10-5 molar derişimlerinin etkileri kümülatif olarak incelendi. Nitrik oksit ile olası bir etkileşimin gözlenmesi amacıyla farklı serilerde ortamda nitrik oksit prekürsörü L-arjinin (10-4 Μ) ve nitrik oksit sentaz inhibitörü L-nitro-arjinin-metil ester (10-4 Μ) bulunduğu halde aynı prosedür tekrarlandı. Histamin H1, H2 ve H3 reseptörlerinin sırasıyla pirilamin (10-6 Μ) ve famotidin (10-6 Μ) tarafından ayrı ayrı bloke edilmesi sonucu elektriksel alan stimülasyonuna verilen kasılma yanıtları düflerken H3 reseptör antagonisti tiyoperamid (10-5 Μ), kasılma yanıtlarını artırdı. Selektif H3 agonisti (R)-α-metilhistaminin kontraktil yanıtlarda belirgin bir azalmaya neden olması ve bu etkilerin selektif H3 reseptör antagonisti tiyoperamid tarafından artırılmış olması nedeniyle histamin H3 reseptörünün muhtemelen H1 ve H2 reseptörlerine zıt yönde etki ettiği ve kontraktil yanıtların inhibisyonuna aracılık ettiği gözlenmiştir. Ortama farklı serilerde nitrik oksit prekürsörü L-arjinin (10-4 Μ) ve nitrik oksit sentaz inhibitörü NG-nitro-L-arjinin metil ester (10-4 Μ) ilave edilmesi sonucunda anlamlı bir farklılık ile karşılaşılmadı. Nitrik oksitin sıçan ileum preparatlarında histamin reseptörlerinin kontraktil aktivitesi üzerine herhangi bir etki etmedi¤i sonucuna varıldı.

The effects of histamine H3 receptors and nitric oxide on electrically stimulated rat ileum contractile responses

The aim of the study is to determine the effects of histamine receptors on the ileum smooth muscle contractions and the role of nitric oxide on these effects. Isolated rat ileum preparations were mounted on organ bath and histamine receptor agonist and antagonists were added to the bath solution, then the electrical field stimulation-induced contractile responses were evaluated. Since NO donor Derivative 28 has H3 antagonistic effect we investigated any interaction between H3 receptors and NO. After blocking one of the histamine receptors H1, H2 and H3; contractile responses were observed. Then, other two receptors were blocked one by one or combination of them, to observe the changes on the contractile responses given to the electrical stimulation. To block histamine receptors; pyrilamine (10-6 Μ) as H1 receptor blocker, famotidine (10-6 Μ) as H2 receptor blocker and thioperamide (10-5 Μ) as H3 receptor blocker and various combination of them were used. All groups were treated with H3 receptor antagonist thioperamide (10-5 Μ) and agonist (R)-α-methylhistamine on 10-8, 10- 7, 10-6 ve 10-5 molar concentrations cumulatively, to observe its mediator effects on contractile responses. To view any possible interaction between histamine H3 receptors and nitric oxide, in the presence of nitric oxide precursore L-arginine (10-4 Μ) and nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester or combination of them the same procedures were carried out. While H1 and H2 receptor blockers decreased the contractile responses given to the electrical field stimulation, H3 receptor blocker increased the responses. Possibly, H3 receptors act contrary to H1 and H2 receptors and mediates inhibition on rat ileum smooth muscle contractility. Selective H3 agonist (R)-α-methylhistamine caused a significant inhibition on the contractile responses where these effects were abolished by selective H3 receptor antagonist thioperamide. In different series nitric oxide precursore L-arginine (10-4 Μ) and nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester (10-4 Μ) were added to the bath solution but no significant differences observed in the contractile responses. In conclusion it was observed that nitric oxide has no effect on histamine receptor mediated contractile activity in rat ileum.

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