Ali KARADENİZ, İlksin PİŞKİN, LEVENT ALTINTAŞ, Dinç EŞSİZ

Tavşan idrar kesesi sirküler ve longitudinal düz kasları üzerine oxybutynin ve tolterodinin etkilerinin in vitro araştırılması

Bu çalışma tavşan idrar kesesinden elde edilen in vitro sirküler ve longitudinal düz kas kasılımları üzerine oxybutynin ve tolterodinin etkilerini araştırmak için yapılmıştır. Araştırmada 4-5 kg ağırlığında 10 adet erkek Yeni Zelanda tavşanı kullanıldı. İzole edilen her bir idrar kesesinden bir adet sirküler ve longitudinal şeritler elde edildi. İlk önce dokulara 1 gramlık gerim uygulanarak ortama alışmaları sağlandı. Uyum süresini takiben submaksimal kasılımın sağlandığı elektrik uyarı düzeyi tespit edildi ve bu uyarılar oxybutynin, tolterodin ve atropinin çeşitli konsantrasyonları varlığında tekrar edildi. İlk önce oxybutynin 10"7M derişimi ortama eklendi ve 15 dk beklendi. Bu sürenin sonunda uyarı verilerek kasılım cevabı elde edildi. Uyarı sonrası doku iki dakikada bir iki kez olmak üzere iki kez yıkanarak başlangıç tonusuna ulaşması sağlandı. Aynı işlemler oxybutyninin (10 6M ve 105M), tolterodin (108M, 107M ve 10"6M) ve atropinin (107M, 10ĞM ve 105M) bildirilen dozlarında tekrarlandı. Sonuç olarak çalışmada oxybutynin ve tolterodinin artan konsantrasyonlarına bağlı olarak elektriksel uyarım ile tavşan sirküler ve longitudinal kaslarda meydana gelen kasılımları engelledikleri görülmüştür. Kasılımların sirküler kaslarda oxybutynin, longitudinal kaslarda ise tolterodin ile daha güçlü olarak engellendiği tespit edilmiştir.

Anahtar Kelimeler:

kas kasılımı, idrar kesesi, ilaçlar, elektrikle uyarım, tavşan

The investigation of in vitro effects of oxybutynin and tolterodine on circulary and longitudinal smooth muscles of rabbit bladder

This study was performed for investigating the effects of oxybutynin and tolterodine on in vitro circulary and longitudinal smooth muscle of rabbit bladder. In this research, ten male New Zeland rabbits weight 4–5 kg were used. One circulary and longitudinal strips were prepared taken from the isolated bladder. At first, 1 g of strecth was applied to tissues adapt to media. Next, fallowing adapt time, the electrical stimulation level which created submaximal contraction was determined and this stimulation was performed by adding different concentrations of oxybutynin, tolterodine and atropine respectively. Firstly 10–7M dosage of oxybutynin (10-7M, 10-6M, 10-5M) was added and waited for 15 minutes. At the end of this period, electrical stimulation was applied to get the contraction response of the tissue. After stimulation, tissue was washed once for every two minute twice and rested, tissue was waited until its starting stretch value. Same processes were performed for oxybutynin (10-6M, 10-5M), tolterodine (10-8M, 10-7M, 10-6M) and atropines’ (10-7M, 10-6M, 10-5M) other dosages. As a result, it was opbserved that oxybutynin and tolterodine due to their increasing concentrations prevented the contractions at circulary and longitudinal smooth muscle of rabbit bladder by electrical stimulation. It was determined that contractions at circulary muscle were prevented more strongly by oxybutynin and contractions at longitudinal muscle were prevented more strongly by tolterodine.

Keywords:

muscle contraction, bladder, drugs, electrical stimulation, rabbits,

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Caulfield MP: Muscarinic receptors--characterization, coupling and function. Pharmacol Ther, 583, 319-379, 1993.
Chapple CR: Muscarinic receptor antagonists in the treatment of overactive bladder. Urology, 555, 33-46, 2000.
Kobayashi S, Ikeda K, Miyata K, Yamada T, Honda K: A method for measurement of muscarinic receptormediated responses in dissociated single colon longitudinal smooth muscle cells. J Pharm oxicol Methods, 45 (3): 199-205, 2001.
Andersson K-E, Appell R, Cardozo L, Chapple C, Drutz H, Fourcroy J, Vela Navarette R, Nishizawa O, Wein A: Pharmacological treatment of urinary incontinence. In, Abrams P, Khoury S, Wein A (Eds): Incontinence, 3rd International Consultation on Incontinence. 21st ed. pp. 811-854. France: Health Publication Ltd, 2005.
Eglen EM, Reddy H, Watson N, Challis RAJ: Muscarinic acetylcholine recptor subtypes in smooth muscle. Trends Pharmacol Sci, 15, 114-119, 1994.
Abrams P, Andersson K-E, Buccafusco JJ, Chapple C, De Groat, WC, Fryer AD, Kay G, Laties A, Nathanson NM, Pasricha PJ, Wein AJ: Muscarinic receptors: Their distribution and function in body systems, and the implications for treating overactive bladder. Br J Pharm, 148, 565-578, 2006.
Wein AJ, Rovner ES: Definition and epidemiology of overactive bladder. Urology, 60 (Suppl 1): 7-12, 2002.
Wein AJ, Longhurst PA, Levin RM: Pharmacologic treatment of voiding dysfunction. In, Munday RA, Stephenson TP, Wein AJ (Eds): Urodynamics: Principles, Practice and Application, 2nd ed. Churchill Livingstone, New York, NY, pp. 43-70, 1994.
Anderson GF, Fredericks CM: Characterization of the oxybutynin antagonism of drug-induced spasms in detrusor. Pharmacology, 151, 31-39, 1977.
Yarker Y, Goa KL, Fritton A: Oxybutynin: A review of its pharmacodynamic and pharmacokinetic properties, and its therapeutic use in detrusor instability. Drugs Aging, 6, 243-262, 1995.
Nilvebrant L, Andersson K-E, Gillberg PG, Stahl M, Sparf B: Tolterodine – A new bladder-selective antimuscarinic agent. Eur J Pharm, 327,195-207, 1997. Longhurst PA, Uvelius B: Pharmacological techniques for the in vitro study of the urinary bladder. J Pharm Toxicol Methods, 45, 91-108, 2001.
Szell EA, Yamamoto T, De Groat WC, Somogyi GT: Smooth muscle and parasympathetic nerve terminals in the rat urinary bladder have different subtypes of alpha1 adrenoceptors. Br J Pharmacol, 130 (7): 1685-1691, 2000.
Andersson K-E, Appell R, Awad S, Chapple C, Drutz H, FBnkbeBner A, Haab F, Vela Navarrete R: Pharmacological treatment of urinary incontinence. In, Abrams P, Cardozo L, Khoury S, Wein A (Eds): Incontinence, 2nd Inter-national Consultation on Incontinence. Plymouth, UK, Plymbridge Distributors Ltd. pp. 479-511, 2002.
Fetscher C, Fleichman M, Schmidt M, Krege S, Michel MC: M3 muscarinic receptors mediate contraction of human urinary bladder. Br J Pharmacol, 136,641–643, 2002.
Andersson KE: Antimuscarinics for treatment of overactive bladder. Lancet Neurol, 3, 46-53, 2004.
Chopin A, Eglen RM, Hegde SS: Pharmacological characterization of muscarinic receptors in rabbit isolated iris sphincter muscle and urinary bladder smooth muscle. Br J Pharmacol, 1245, 883-888, 1998.
Wust M, Averbeck B, Reif S, Brater M, Ravens U: Different responses to drugs against overactive bladder in detrusor muscle of pig, guinea pig and mouse. Eur J Pharmacol, 454 (1): 59-69, 2002.
Uckert S, Stief CG, Odenthal KP, Truss MC, Lietz B, Jonas U: Responses of isolated normal human detrusor muscle to various spasmolytic drugs commonly used in the treatment of the overactive bladder. Arzneimittelforschung, 505, 456-460, 2000.
Kato K, Kondo A, Saito M, Miyake K, Wein AJ, Levin RM: In vitro intravesical instillation of anticholinergic, anti-spasmodic and calcium blocking agents to decrease bladder contractility. Urol Int, 47 (Suppl 1): 36-8, 1991.
Levin RM, Wein AJ: Direct measurement of the anticholinergic activity of a series of pharmacological compounds on the canine and rabbit urinary bladder. J Urol, 1282, 396-398, 1982.
Nelson CP, Gupta P, Napier CM, Nahorski SR, Challiss RA: Functional selectivity of muscarinic receptor antagonists for inhibition of M3-mediated phosphoinositide responses in guinea pig urinary bladder and submandibular salivary gland. J Pharmacol Exp Ther, 310 (3): 1255-1265, 2004.
Angelico P, Velasco C, Guarneri G, Leonardi A, Testa R: Urodynamic effects of oxybutynin and tolterodine in conscious and anesthetized rats under different cystometrographic conditions. BMC Pharmacol, 5, 14, 2005.
Yamanishi T, Chapple CR, Chess-Williams R: Which muscarinic receptor is important in the bladder? World J Urol, 195, 299-306, 2001.
Arisco AM, Kraus SR: Does intravesical atropine have equivalent efficacy to oral oxybutynin in the treatment of detrusor overactivity? Nat Clin Pract Urol, 4 (10): 538- 539, 2007.
Levin RM, Whitbeck C, Borow A, Burden O, Legett RE: Effectiveness of vaginally administered oxybutynin on rabbit bladder function. Urology, 616, 1273-1277, 2003. KARADENİZ, PİŞKİN, ALTINTAŞ, EŞSİZ 7