Antikolinesteraz ilaçların sıçan ileum düz kasında betanekol ile uyarılan kasılma yanıtlarına etkisi

Günümüzde halen tedavi amaçlı olarak intestinal sistem ve mesane düz kaslarının atonisinde, glokomda, myastenia graviste ve kompetitif nöromuskuler kas gevşeticilerin etkilerinin sonlandırılmasında kullanılan antikolinesterazlar, bu gibi kolinerjik aktivitenin azaldığı durumlarda reseptörler üzerine selektif etkiler oluşturmaktan ziyade ACh konsantrasyonunu arttırarak dolaylı etkileriyle nonselektif olarak hem muskarinik hem de nikotinik etkiler oluştururlar. Son yıllarda yapılan bazı çalışmalarda antikolinesteraz ilaçların doğrudan antimuskarinik etkiler de oluşturabileceği bildirilmiştir. Biz de çalışmamızda bu amaçla, her bir Wistar albino sıçandan hazırlanan ileum düz kas preparatlarında muskarinik agonistik etkili betanekol ile oluşturulan kasılma yanıtları üzerine neostigmin, edrofonyum ve piridostigminin doza bağımlı etkilerini inceledik. Antikolinesterazların hiçbirisi ilk üç derişimlerinde betanekol kasılma yanıtlarında bir güçlenmeye yol açmadı (p > 0,05; eşleştirilmiş Student’s t test). Fakat 1000μM’lık en yüksek derişimlerinde, neostigmin, edrofonyum ve piridostigmin, ileum düz kas preparatlarında betanekol ile uyarılan düz kas kasılmalarını zayıflattı (p ≤ 0,05; paired samples t test). Sonuçlar antikolinesterazların sıçan ileum preparatlarındaki kolinerjik kasılma yanıtları üzerinde dual etkili olmadıklarını düşündürmektedir. Antikolinesterazlar yüksek dozlarında, ileum düz kas kasılmaları üzerinde antimuskarinik etkilere yol açabilirler.

Anahtar Kelimeler:

Sıçan, Wistar, Betanekol, Modeller, hayvan, Kolinesteraz inhibitörleri, Kas, düz, Kas kasılması, İleum

The effects of anticholinesterase drugs on bethanechol-induced contractile responses in rat ileum smooth muscle

At present, anticholinesterase drugs are valuable as therapeutic agents when cholinergic activity decreased in cases such as glokom, myastenia gravis and postoperative period which induces atony in bladder and intestinal smooth muscles. In these conditions anticholinesterases are expected to increase the levels of acetylcholine by inhibiting the enzyme acetylcholinesterase, thus they can exhibit both muscarinic and nicotinic effects indirectly rather than constituting a direct effect on muscarinic receptors. But recently, it has been shown that anticholinesterase drugs may exhibit a dose-dependent antimuscarinic effect by interacting with muscarinic receptors directly. According to these results, we investigated the dose-dependent effects of anticholinesterases on bethanechol-induced contractile responses at ileum smooth muscle preparations. Our results show that none of the three anticholinesterases did cause any potentialization on contractile responses for bethanechol at their first three concentrations (p > 0,05; paired samples t test). But at their highest concentration such as 1000 μM, neostigmine, edrophonium and piridostigmine attenuated the bethanechol induced contractile responses (p≤ 0,05; paired samples t test). These results suggest that anticholinesterases do not have dual effects on bethanechol induced contractile responses in rat ileum smooth muscle preparations. Larger doses of anticholinesterases may evoke antimuscarinic effects on ileum smooth muscle contractions.

Keywords:

Rats, Wistar, Bethanechol, Models, Animal, Cholinesterase Inhibitors, Muscle, Smooth, Muscle Contraction, Ileum,

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