Antikolinesteraz ilaçların sıçan mide fundus ve ileum düz kasında elektriksel alan stimülasyonu aracılı kasılma yanıtları üzerine anti-muskarinik etkileri

İntestinal sistem düz kas kasılmasından dolayısıyla da motiliteden başlıca sorumlu olan otonom sinir sisteminin parasempatik bölümüdür ve bu etkinin gelişimine, fizyolojik veya elektriksel stimülasyon gibi bir uyarana bağlı olarak eksitasyona uğrayan parasempatik liflerden salıverilen asetilkolin aracılık eder. Antikolinesteraz ilaçlar ise kolinerjik yolaklarda asetilkolinesterazı inhibe etmek suretiyle yıkımını önledikleri asetilkolinin düzeylerini artırarak dolaylı etkileriyle hem muskarinik hem de nikotinik etkiler oluştururlar. Yapılan bazı çalışmalarda asetilkolinesteraz inhibitörü ilaçların beklenenin aksine antimuskarinik etkiler de oluşturduğu bildirilmiştir. Biz de bu çalışmada neostigmin, edrofonyum ve piridostigmin gibi etki süreleri farklı olan antikolinesteraz ilaçların, Wistar albino sıçanlardan izole edilen mide fundus ve ileum düz kas preparatlarında, bir direkt stimülasyon tekniği olan Elektriksel Alan Stimülasyonu(EAS) ile uyarılan kasılma yanıtları üzerine olası antimuskarinik etkilerini incelemeyi amaçladık. Neostigmin ve piridostigminin her ikisi de ilk üç derişimlerinde (sırasıyla 1, 10 ve 100 μM), EAS’na bağlı kasılma yanıtlarının E maks değerlerini arttırdı, ancak sadece mide fundus striplerindeki değişiklikler istatistiksel olarak anlamlı bulundu. 1mM gibi en yüksek derişimlerinde, neostigmin ve piridostigmin EAS ile uyarılan düz kas kasılmalarını zayıflattı ve bir antimuskarinik etkiye yol açtı (p ≤ 0,05; eşleştirilmiş Student’s t test). Bunun aksine, edrofonyum dört derişiminden hiçbirisinde EAS ile uyarılan kas kasılmaları üzerinde anlamlı bir etki oluşturmadı (p > 0,05; eşleştirilmiş Student’s t test). Neostigmin ve piridostigminin yüksek dozları, edrofonyumdan farklı olarak intestinal düz kas kasılmaları üzerinde antimuskarinik etkilere yol açmaktadır.

Anahtar Kelimeler:

Sıçan, Wistar, Modeller, hayvan, Mide fundusu, Kas, düz, Muskarinik antagonistler, Kas kasılması, İleum, Elektrikle uyarma, Kolinesteraz inhibitörleri

The antimuscarinic effects of anticholinesterase drugs on electrical field stimulation-induced contractile responses in rat gastric fundus and ileum smooth muscle

Parasympathetic component of autonomic nervous system is known as involving in majority of intestinal smooth muscle contractions and motility. Acetylcholine can be released from parasympathetic nerve terminals by an excitation which is formed by a physiological or an electrical stimulation in order to elicit smooth muscle contractions. Anticholinesterase drugs are expected to increase the levels of acetylcholine in cholinergic synapses via inhibiting the enzyme acetylcholinesterase. In recent studies, it has been shown that anticholinesterase drugs may cause an antimuscarinic effect on the contrary of their usual effects such as amplifying of cholinergic transmission. In this study, we investigated the antimuscarinic effects of neostigmine, edrophonium and piridostigmine on gastric fundus and ileum smooth muscle preparations isolated from Wistar albino rats. The contactions were induced by using electrical field stimulation (EFS) which is a direct stimulation technique. Both neostigmine and piridostigmine increased the E max values of contractile responses for EFS at their first three concentrations; but only the changes in gastric fundus strips has found significant as statistically. At their highest concentration such as 1000 μM, both neostigmine and piridostigmine attenuated the EFS induced smooth muscle contractions and caused an antimuscarinic effect (p ≤ 0,05; paired samples Student’s t test). In contrast, edrophonium had no effect on EFS induced smooth muscle contractions, at none of its four concentrations as statistically. Our results suggest that larger doses of neostigmine and piridostigmine, but not edrophonium, may evoke antimuscarinic effects on intestinal smooth muscle contractions.

Keywords:

Rats, Wistar, Models, Animal, Gastric Fundus, Muscle, Smooth, Muscarinic Antagonists, Muscle Contraction, Ileum, Electric Stimulation, Cholinesterase Inhibitors,

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