NDLI: Glucose-dependent enhancement of diabetic bladder contraction is associated with a rho kinase-regulated protein kinase C pathway.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Nobe, Koji Yamazaki, Taigi Tsumita, Naoki Hashimoto, Terumasa Honda, Kazuo
Description	Country affiliation: Japan Author Affiliation: Nobe K ( Department of Pharmacology, School of Pharmaceutical Sciences, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan. kojinobe@pharm.showa-u.ac.jp)
Abstract	Urinary bladder dysfunction, which is one of the most common diabetic complications, is associated with alteration of bladder smooth muscle contraction. However, details regarding the responses under high-glucose (HG) conditions in diabetes are poorly understood. The objective of this study was to identify a relationship between extracellular glucose level and bladder smooth muscle contraction in diabetes. Bladder smooth muscle tissues were isolated from spontaneously type II diabetic (ob/ob mouse; 16-20 weeks of age, male) and age-matched control (C57BL mouse) mice. Carbachol (CCh) induced time- and dose-dependent contractions in ob/ob and C57BL mice; however, maximal responses differed significantly (14.34 +/- 0.32 and 12.69 +/- 0.22 mN/mm(2) after 30 microM CCh treatment, respectively; n = 5-8). Pretreatment of bladders under HG conditions (22.2 mM glucose; concentration is twice that of normal glucose for 30 min) led to enhancement of CCh-induced contraction solely in diabetic mice (15.9 +/- 0.26 mN/mm(2); n = 5). Basal extracellular glucose-dependent enhancement of bladder contraction in diabetes was documented initially in this study. The correlation between intracellular calcium concentration and contraction was enhanced only in the ob/ob mouse. This enhancement of contraction and total protein kinase C (PKC) activity were inhibited by pretreatment with not only a PKC inhibitor (rottlerin) but also with a rho kinase inhibitor, fasudil [1-(5-isoquinolinesulfonyl)homopiperazine HCl]. These reagents also suppressed the differences between ob/ob and C57BL mouse bladder contractions under HG conditions. The data indicated that glucose-dependent enhancement of contraction in diabetic bladder is involved in the activation of the rho kinase and calcium-independent PKC pathways. This dysfunction may contribute to bladder complications such as detrusor overactivity and reduced bladder capacity in diabetes.
File Format	HTM / HTML
ISSN	00223565
Issue Number	3
Volume Number	328
e-ISSN	15210103
Journal	Journal of Pharmacology and Experimental Therapeutics
Language	English
Publisher	American Society for Pharmacology and Experimental Therapeutics
Publisher Date	2009-03-01
Publisher Place	United States
Access Restriction	Subscribed
Subject Keyword	Research Support, Non-u.s. Gov't Male Phospholipids Glucose Discipline Pharmacology Blood Journal Article Diabetes Mellitus, Type 2 Mice, Inbred C57bl Blood Glucose Pharmacology Triglycerides Rho-associated Kinases Metabolism Drug Effects Cholesterol Physiopathology Muscle, Smooth Muscle Contraction Animals Carbachol Discipline Therapeutics Fatty Acids, Nonesterified Mice, Obese Mice Urinary Bladder Protein Kinase C
Content Type	Text
Resource Type	Article
Subject	Molecular Medicine Pharmacology

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