Urinary bladder relaxation through activation of opioid μ-receptors induced by loperamide is increased in diabetic rats

L. M. Lee, C. S. Lin, H. H. Chung, K. C. Lin, J. T. Cheng

Research output: Contribution to journalArticle

5 Citations (Scopus)

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 + (K ATP) 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 K ATP channels.

Original languageEnglish
Pages (from-to)323-328
Number of pages6
JournalExperimental and Clinical Endocrinology and Diabetes
Volume120
Issue number6
DOIs
Publication statusPublished - 2012

Fingerprint

Loperamide
Opioid Receptors
Urinary Bladder
Streptozocin
Adenosine Triphosphate
Cyclic AMP-Dependent Protein Kinases
Cyclic AMP
Adenylate Kinase
Overactive Urinary Bladder
Muscle Relaxation
Phosphodiesterase Inhibitors
Glyburide
Colforsin
Protein Kinase Inhibitors
Naloxone
Adenylyl Cyclases
Acetylcholine
Wistar Rats
Injections

Keywords

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

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism
  • Internal Medicine

Cite this

Urinary bladder relaxation through activation of opioid μ-receptors induced by loperamide is increased in diabetic rats. / Lee, L. M.; Lin, C. S.; Chung, H. H.; Lin, K. C.; Cheng, J. T.

In: Experimental and Clinical Endocrinology and Diabetes, Vol. 120, No. 6, 2012, p. 323-328.

Research output: Contribution to journalArticle

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