Antikolinesteraz ilaçların sıçan mide fundus düz kası üzerine anti-muskarinik etkileri

Çalışmamızda neostigmin, piridostigmin ve edrofonyumun yüksek dozlarında sıçan mide fundus düz kas dokularındaki muskarinik reseptörleri inhibe edip etmediklerini ve bu ilaçların sıçan intestinal düz kas kasılmaları üzerine olası dual etkilerini inceledik. Çalışmamızın başlangıcında ilk olarak betanekole kümülatif olarak kontrol kasılma yanıtları alındı. Takiben antikolinesterazların her bir konsantrasyonu sonrasında betanekol için kümülatif derişim-yanıt eğrileri elde edildi. Antikolinesterazlardan hiçbirisi ilk üç derişimlerinde (sırasıyla 1, 10 ve 100 µM), betanekol kasılma yanıtlarında herhangi bir güçlenmeye yol açmadı (p >0,05). Fakat 1mM’lık en yüksek derişimlerinde, neostigmin, edrofonyum ve piridostigmin, mide düz kas striplerinde betanekolle uyarılan düz kas kasılmalarını zayıflattı (p ≤0,05; eşleştirilmiş Student’s t test). Sonuçlar antikolinesterazların sıçan mide fundus preparatlarındaki kolinerjik kasılma yanıtları üzerinde dual etkili olmadıklarını düşündürmektedir. Antikolinesterazlar yüksek dozlarında, mide fundus düz kas kasılmaları üzerinde antimuskarinik etkilere yol açabilirler.

The antimuscarinic effects of anticholinesterase drugs on rat gastric fundus smooth muscle

We investigated whether neostigmine, piridostigmine and edrophonium in larger doses inhibit muscarinic receptors of rat gastric fundus and whether those drugs have dual effects on rat intestinal smooth muscle contractions. Initially control contractile responses in a cumulative manner obtained for bethanechol, Following this, four different concentrations of each anticholinesterases (respectively 1, 10, 100 and 1000 µM) injected into the organ bath solution where smooth muscle strips attached. After each concentration of anticholinesterases, cumulative dose-response curves for bethanechol has been obtained. Our results show that none of the three anticholinesterases did cause any potentialization on contractile responses for bethanechol at their first three concentrations (respectively 1, 10 and 100 µM). 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 of rat gastric fundus smooth muscle preparations. Larger doses of anticholinesterases may evoke antimuscarinic effects on intestinal smooth muscle contractions.

___

  • 1. Goodman Gilman A; Hardman JG, Limbird LE. Goodman & Gilman’s The Pharmacological Basis of Therapeutics. Ninth Edition, McGraw-Hill Medical Publishing Division; 1996. p. 105-6, 161-63, 171.
  • 2. Katzung BG. Basic & Clinical Pharmacology. Cholinoceptor-activating & Cholinesterase-inhibiting drugs. Seventh Edition, McGraw-Hill Medical Publishing Division; 1998. p. 93-96.
  • 3. Kenakin TP, Beek D: Self – cancellation of Drug Properties as a mode of organ selectivity: the antimuscarinic effects of ambenonium. American Society for Pharmacology and Experimental Therapeutics 1985; 232: 732-40.
  • 4. Endou M, Tanito Y, Okumura F: A comparison between chronotropic effects of neostigmine and edrophonium in isolated guinea-pig right atrium. Pharmacology and Exp. Therapeutics 1997; 282: 1480-1486.
  • 5. Pharmacological Experiments on Isolated Preparations. Experiments with Intestinal Smooth Muscle. University of Edinburgh, Preface by PERRY W. L. M., Churchill Livingstone, Edinburgh, LONDON and NEW YORK; 1970. p. 58 – 62, 88 – 89.
  • 6. Galligan JJ, Burks TF: Cholinergic neurons mediate intestinal propulsion in the rat. The Journal of Pharmacology and Experimental Therapeutics 1986; 238: 594-598
  • 7. Kayaalp SO. Rasyonel tedavi yönünden Tıbbi Farmakoloji. Kolinomimetik ilaçlar: Parasempatomimetik ilaçlar ve antikolinesterazlar. Cilt II, sekizinci baskı, Ankara: Feryal Matbaacılık; 1998. p. 1136-52.
  • 8. Tsuda A, Shibata O, Saito M et al: A dose-response study of anticholinesterase drugs on contractile and phosphatidylinositol responses of rat trachea. Anasthesia & Analgesia 2001; 92: 100-105.
  • 9. Deschamps A, Backman SB, Novak V et al: Effects of the anticholinesterase edrophonium on spectral analysis of heart rate and blood pressure variability in humans. J Pharmacol Exp Ther 2002; 300: 112-117.
  • 10. Yost CS, Maestrone E: Clinical concentrations of edrophonium enhance desensitization of the nicotinic acetylcholine receptor. Anesth Analg 1994; 78: 520-526.
  • 11. Sherby SM, Eldefrawi AT, Albuquerque EX et al: Comparison of the actions of carbamate anticholinesterases on the nicotinic acetylcholine receptor. Mol Pharmacol 1985; 27: 343-348.
  • 12. Stengel PW, Cohen ML: M1 receptormediated nitric oxide-dependent relaxation unmasked in stomach fundus from M3 receptor knockout mice. J Pharmacol Exp Ther 2003; 304: 675-682.
  • 13. Shehnaz D, Ansari ZK, Ehlert FJ: Acetylcholine-induced desensitization of the contractile response to histamine in guinea-pig ileum is prevented by either pertusis toxin treatment or by selective inactivation of muscarinic M3 receptors. J Pharmacol Exp Ther 2001; 297: 1152-1159.
  • 14. Stengel PW, Gomeza J, Wess J, Cohen ML: M(2) and M(4) receptor knockout mice: muscarinic receptor function in cardiac and smooth muscle in vitro. J Pharmacol Exp Ther 2000; 292: 877-885.
  • 15. Tanito Y, Miwa T, Endou M et al: Interaction of edrophonium with muscarinic acetylcholine M2 and M3 receptors. Anesthesiology 2001; 94: 804-814.
  • 16. Eglen RM, Adham N, Whiting RL: Acute desensitization of muscarinic receptors in the isolated guinea-pig ileal longitudinal muscle. J Auton Pharmacol 1992; 12: 137-48.
Dicle Tıp Dergisi-Cover
  • ISSN: 1300-2945
  • Yayın Aralığı: Yılda 4 Sayı
  • Başlangıç: 1963
  • Yayıncı: Cahfer GÜLOĞLU