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Exp Clin Endocrinol Diabetes 2012; 120(06): 323-328
DOI: 10.1055/s-0031-1295473
Article
© J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart · New York

Urinary Bladder Relaxation Through Activation of Opioid μ-Receptors Induced by Loperamide is Increased in Diabetic Rats

L.-M. Lee   *
1   Department of Urology, College of Medicine, Taipei Medical University – Wan-Fang Hospital, Wang-Fang, Taipei City, Taiwan
,
C.-S. Lin   *
2   Department of Surgery, Chi-Mei Medical Center Liouying, Liou-Ying, Tainan City, Taiwan
,
H.-H. Chung
3   Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan City, Taiwan
,
K.-C. Lin
4   Department of Medical Research and Department of Neurology, Chi-Mei Medical Center, Yong Kang, Tainan City, Taiwan
5   Institute of Biotechnology, Southern Taiwan University, Yong Kang, Tainan City, Taiwan
,
J.-T. Cheng
3   Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan City, Taiwan
4   Department of Medical Research and Department of Neurology, Chi-Mei Medical Center, Yong Kang, Tainan City, Taiwan
› Author Affiliations
Further Information

Publication History

received 19 September 2011
first decision 09 November 2011

accepted 11 November 2011

Publication Date:
20 December 2011 (online)

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Abstract

The role of opioid μ-receptor activation in the improvement of overactive bladder (OAB) remains obscure. Thus, we used loperamide to activate opioid μ-receptors for urinary bladder relaxation and compared the differences between normal and diabetic rats. Urinary bladder strips were isolated from Wistar rats that did or did not receive streptozotocin (STZ) injection for analysis of isometric tension. Samples were contracted with either acetylcholine (ACh) or KCl, and decrease of muscle tone (relaxation) was characterized after treatment with loperamide. Specific antagonists were used for pretreatment to compare the changes in loperamide-induced relaxation. As compared with normal rats, loperamide produced a more marked relaxation in bladder strips of STZ-diabetic rats in a dose-dependent manner. This relaxation by loperamide was attenuated by glibenclamide at a dose sufficient to block ATP-sensitive K+ (KATP) channels. In addition, this action of loperamide was abolished by protein kinase A (PKA) inhibitor and enhanced by the inhibitor of phosphodiesterase for cyclic AMP (cAMP). However, treatment with forskolin, an activator of adenylate cyclase, resulted in no difference in relaxation in normal and diabetic rats. The action of loperamide was abolished by cyprodime and naloxone, but was not modified by naloxonazine at a dose sufficient to block opioid μ-1 receptors. A higher expression of opioid μ-receptors in diabetic rats was observed. Our results suggest that the increase in urinary bladder relaxation in STZ-diabetic rats by loperamide is mainly induced through activation of opioid μ-receptors linked to the cAMP-PKA pathway to open KATP channels.

Key words

ATP-sensitive K+ channels - isometric tension - loperamide - opioid μ-receptors - overactive bladder
*

*  These authors contributed equally.


 

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