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 language | English |
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Pages (from-to) | 323-328 |
Number of pages | 6 |
Journal | Experimental and Clinical Endocrinology and Diabetes |
Volume | 120 |
Issue number | 6 |
DOIs | |
Publication status | Published - 2012 |
Keywords
- ATP-sensitive K channels
- isometric tension
- loperamide
- opioid μ-receptors
- overactive bladder
ASJC Scopus subject areas
- Internal Medicine
- Endocrinology, Diabetes and Metabolism
- Endocrinology