Öz
Bu araştırmada, diazepam ve baklofenin kobaylarda sidik kesesi düz kası üzerine etkileri incelenmiştir. Çalışmada 250300 gram ağırlığında 15 kobaydan izole edilen her bir sidik kesesinden hazırlanan şerit şeklinde preparatlar, içerisinde “Tyrode” çözeltisi bulunan organ banyosuna yerleştirildi. Asetilkolinin (ACh) yalnız (10-5M, 3x10-5M, 10-4M), diazepam (10-6M, 10-5M, 10M) ve baklofenin (10-5M, 10-4M, 10-3M) varlığında denenmesiyle oluşturduğu cevaplar alındı. Sidik kesesi düz kasında Ach’nin üç farklı konsantrasyonunun oluşturduğu cevapların amplitütlerinde, en büyük kasılımı 10-4M’lık ACh’nin verdiği belirlendi. Diazepamın en yüksek dozunun (10-4M) varlığında ACh’nin farklı üç konsantrasyonuna alınan cevapların, ACh’nin yalnız kullanılmasına göre kasılımları %60-75 oranında azalttığı tespit edildi. Latent sürelerde ise ACh’nin iki dozuna (10-5M, 3x10-5M) göre en büyük derişiminin (10-4M) verdiği cevap süresinin %59-64 kısaldığı görüldü. Diazepamın (10-4M), kobay sidik kesesi düz kası kasılımlarını, artan ACh konsantrasyonuyla yarışmalı bir şekilde baskılayabildiği saptandı. Baklofenin üç farklı dozunun varlığında, ACh’nin üç farklı derişiminin oluşturduğu cevaplarda ise ACh’nin yalnız denenmesine göre hem latent süreler hem de kasılımlarda önemli farklılığın bulunmadığı gözlemlendi. Sonuç olarak, in vitro koşullarda kobay sidik kesesi düz kasında ACh kaynaklı kasılımları diazepamın doza bağlı olarak inhibe ettiği, baklofenin ise bu kasılımları etkilemediği belirlendi
Anahtar Kelimeler
Kaynakça
- Ayyat FM, Lloyd LK, Kuhlemeier KV (1984): Effect of skeletal muscle relaxants on bladder smooth muscle. J Urology, 132, 372-375.
- Chapple CR (2000): Muscarinic receptor antagonists in the treatment of overactive bladder. Urology, 55, 33-46.
- Clanachan AS, Marshall RJ (1980): Potentiation of effects of adenosine on isolated cardiac and smooth muscle by diazepam. Br J Pharmacol. 71, 459-466.
- Doyle PT, Briscoe CE (1976): The effects of drugs and anaesthetic agents on the urinary bladder and sphincters. Br J of Urology, 48, 329-335.
- Giglio D, Delbro DS, Tobin G (2001): On the functional role of muscarinic M2, receptors in cholinergic and purinergic responses in the rat urinary bladder. Eur J Pharm, 428, 357-364.
- Giotti A, Luzzi S, Spagnesi S, Ziletti L (1983): GABAA and GABAB receptor mediated effects in guinea-pig ileum. Br J Pharmacol, 78, 469-478.
- Gosling JA, Gilpin SA, Dixon JS, Gilpin CJ (1986): Decrease in the autonomic innervation of human detrusor muscle in outflow obstruction. J Urology, 136, 501-504.
- Ha JH, Lee KY, Kim WJ (1993): The action of diazepam in the isolated rat detrusor muscle. J Urology, 150, 229- 234.
- Hullihan JP, Spector S, Taniguchi T, Wang JKT (1983): The binding of [3H] -diazepam to guinea-pig ileal longitudinal muscle and the in vitro inhibition of contraction by benzodiazepines. Br J Pharmacol, 78, 321- 327.
- Ishii K, Kano M, Akutagawa M, Makino M, Tanaka T, Ando J (1982): Effects of flurazepam and diazepam in isolated guinea-pig taenia coli and longitudinal muscle. Eur J Pharm, 83, 329-333.
- Kobayashi S, Ikeda K, Miyata K, Yamada T, Honda K (2001): A method for measurement of muscarinic receptor- mediated responses in dissociated single colon longitudinal smooth muscle cells. J Pharm and Toxicol Methods, 45, 199-205.
- Kubota K, Sugaya K, Sunagane N, Matsuda I, Uruno T (1985): Cholecystokinin antagonism by benzodiazepines in the contractile response of the isolated guinea-pig gallbladder. Eur J Pharm, 110, 225-231.
- Kusunoki M, Taniyama K, Tanaka C (1984): Neuronal GABA release and GABA inhibition of ACh release in guinea pig urinary bladder.Am Physiol Soc, 502-509.
- Longhurst PA, Uvelius B (2001): Pharmacological techniques for the in vitro study of the urinary bladder. J Pharm and Toxicol Methods, 45, 91-108.
- Maggi AC, Santicioli P, Meli A (1985a): GABAA and GABAB receptors in detrusor strips from guinea-pig bladder dome. J Autom Pharmac, 5, 55-64.
- Maggi AC, Santicioli P, Meli A (1985b): Dual effect of GABA on the contractile activity of the guinea-pig isolated urinary bladder. J Autom Pharmac, 5, 131-141.
- Meldrum LA, Bojarski JC, Calam J (1986): Effects of benzodiazepines on responses of guinea-pig ileum and gall-bladder and rat pancreatic acini to cholecystokinin. Eur J Pharm, 123, 427-432.
- Pencheva N, Itzev D, Milanov P (1999): Comparison of γ-aminobutyric acid effect in different parts of the cat ileum. Eur J Pharm, 368, 49-56.
- Rampe D, Triggle DJ (1987): Benzodiazepine interactions at neuronal and smooth muscle Ca2+ channels. Eur J Pharm, 134, 189-197.
- Sağmanlıgil V, Etlik Ö, Pişkin İ, Tomur A (1999): The effects of cyclophosphamide and its uroprotective agents, mesna and hyperbaric oxygen, on motility of urinary bladder in guinea pigs. Acta Vet Hungarica, 47, 451-460.
- Santicioli P, Maggi CA, Meli A (1984): GABAB receptor mediated inhibition of field stimulation-induced contraction of rabbit bladder muscle in-vitro. J Pharm Pharmacol, 36, 378-381.
- Shirakawa J, Taniyama K, Iwai S, Tanaka C (1988): Regulation of [ 3H]GABA release from strips of guinea pig urinary bladder. Am J Physiol Soc, 888-893.
- Steers WD, Chai TC (1996): Neurophysiology of micturiation and continence. Urol Clin N Am, 23, 221.
- Taniyama K, Kusunoki M, Tanaka C (1983): γ-Amino- butyric acid inhibits motility of the isolated guinea-pig urinary bladder. Eur J Pharm, 89, 163-166. Geliş tarihi: 23.09.2003 / Kabul tarihi: 05.02.2004
Öz
This study was carried out to observe the effects of diazepam and baclofen on the urinary bladder smooth muscle of guinea pigs. In the study, 15 guinea pigs weighing 250-300 g were used. The ribbon-like tissue samples were prepared from the isolated urinary bladder. The tissue strips were placed into the isolated organ bath as in Tyrode solution. The contractions were induced by acetylcholine (ACh) at the concentrations of 10-5M, 3x10-5M and 10-4M alone and in the presences of diazepam and baclofen at the concentrations 10-6M, 10-5M, 10-4M and 10-5M, 10-4M, 10-3M respectively. As a result, it was observed that of ACh after using at three different concentrations on the urinary bladder, the biggest contraction was obtained with 10-4M ACh. On the other hand, the contraction responses obtained with acetylcoline at three different concentrations in the presence of the highest concentration of diazepam (10-4M) were decreased at the rate of 60-75% compared to those obtained in using ACh in same concentrations alone. In the matter of latent duration, it was decreased with 10-4M ACh at the rate of 59-64% compared to the other doses (3x10-5M and 10-4M). It was noticed that diazepam (10-4M) could decrease the motility of urinary bladder by competing with increased concentrations of ACh. On the other hand, there were not significant differences between using ACh at three different concentrations alone and in the presence of three concentrations of baclofen in both latent durations and amplitudes. As a conclusion, it was observed that diazepam inhibits ACh-induced contractions in the smooth muscle of urinary bladder of guinea pig in vitro depending on its concentrations, while baclofen at three different concentrations does not affect those contractions
Anahtar Kelimeler
Kaynakça
- Ayyat FM, Lloyd LK, Kuhlemeier KV (1984): Effect of skeletal muscle relaxants on bladder smooth muscle. J Urology, 132, 372-375.
- Chapple CR (2000): Muscarinic receptor antagonists in the treatment of overactive bladder. Urology, 55, 33-46.
- Clanachan AS, Marshall RJ (1980): Potentiation of effects of adenosine on isolated cardiac and smooth muscle by diazepam. Br J Pharmacol. 71, 459-466.
- Doyle PT, Briscoe CE (1976): The effects of drugs and anaesthetic agents on the urinary bladder and sphincters. Br J of Urology, 48, 329-335.
- Giglio D, Delbro DS, Tobin G (2001): On the functional role of muscarinic M2, receptors in cholinergic and purinergic responses in the rat urinary bladder. Eur J Pharm, 428, 357-364.
- Giotti A, Luzzi S, Spagnesi S, Ziletti L (1983): GABAA and GABAB receptor mediated effects in guinea-pig ileum. Br J Pharmacol, 78, 469-478.
- Gosling JA, Gilpin SA, Dixon JS, Gilpin CJ (1986): Decrease in the autonomic innervation of human detrusor muscle in outflow obstruction. J Urology, 136, 501-504.
- Ha JH, Lee KY, Kim WJ (1993): The action of diazepam in the isolated rat detrusor muscle. J Urology, 150, 229- 234.
- Hullihan JP, Spector S, Taniguchi T, Wang JKT (1983): The binding of [3H] -diazepam to guinea-pig ileal longitudinal muscle and the in vitro inhibition of contraction by benzodiazepines. Br J Pharmacol, 78, 321- 327.
- Ishii K, Kano M, Akutagawa M, Makino M, Tanaka T, Ando J (1982): Effects of flurazepam and diazepam in isolated guinea-pig taenia coli and longitudinal muscle. Eur J Pharm, 83, 329-333.
- Kobayashi S, Ikeda K, Miyata K, Yamada T, Honda K (2001): A method for measurement of muscarinic receptor- mediated responses in dissociated single colon longitudinal smooth muscle cells. J Pharm and Toxicol Methods, 45, 199-205.
- Kubota K, Sugaya K, Sunagane N, Matsuda I, Uruno T (1985): Cholecystokinin antagonism by benzodiazepines in the contractile response of the isolated guinea-pig gallbladder. Eur J Pharm, 110, 225-231.
- Kusunoki M, Taniyama K, Tanaka C (1984): Neuronal GABA release and GABA inhibition of ACh release in guinea pig urinary bladder.Am Physiol Soc, 502-509.
- Longhurst PA, Uvelius B (2001): Pharmacological techniques for the in vitro study of the urinary bladder. J Pharm and Toxicol Methods, 45, 91-108.
- Maggi AC, Santicioli P, Meli A (1985a): GABAA and GABAB receptors in detrusor strips from guinea-pig bladder dome. J Autom Pharmac, 5, 55-64.
- Maggi AC, Santicioli P, Meli A (1985b): Dual effect of GABA on the contractile activity of the guinea-pig isolated urinary bladder. J Autom Pharmac, 5, 131-141.
- Meldrum LA, Bojarski JC, Calam J (1986): Effects of benzodiazepines on responses of guinea-pig ileum and gall-bladder and rat pancreatic acini to cholecystokinin. Eur J Pharm, 123, 427-432.
- Pencheva N, Itzev D, Milanov P (1999): Comparison of γ-aminobutyric acid effect in different parts of the cat ileum. Eur J Pharm, 368, 49-56.
- Rampe D, Triggle DJ (1987): Benzodiazepine interactions at neuronal and smooth muscle Ca2+ channels. Eur J Pharm, 134, 189-197.
- Sağmanlıgil V, Etlik Ö, Pişkin İ, Tomur A (1999): The effects of cyclophosphamide and its uroprotective agents, mesna and hyperbaric oxygen, on motility of urinary bladder in guinea pigs. Acta Vet Hungarica, 47, 451-460.
- Santicioli P, Maggi CA, Meli A (1984): GABAB receptor mediated inhibition of field stimulation-induced contraction of rabbit bladder muscle in-vitro. J Pharm Pharmacol, 36, 378-381.
- Shirakawa J, Taniyama K, Iwai S, Tanaka C (1988): Regulation of [ 3H]GABA release from strips of guinea pig urinary bladder. Am J Physiol Soc, 888-893.
- Steers WD, Chai TC (1996): Neurophysiology of micturiation and continence. Urol Clin N Am, 23, 221.
- Taniyama K, Kusunoki M, Tanaka C (1983): γ-Amino- butyric acid inhibits motility of the isolated guinea-pig urinary bladder. Eur J Pharm, 89, 163-166. Geliş tarihi: 23.09.2003 / Kabul tarihi: 05.02.2004
Ayrıntılar
| Birincil Dil | Türkçe |
|---|---|
| Bölüm | Araştırma Makalesi |
| Yazarlar | |
| Yayımlanma Tarihi | 1 Eylül 2004 |
| Yayımlandığı Sayı | Yıl 2004Cilt: 51 Sayı: 3 |