Impaired M3 and enhanced M2 muscarinic receptor contractile function in a streptozotocin model of mouse diabetic urinary bladder

• Published in: Naunyn-Schmiedeberg's archives of pharmacology 2010-05, Vol.381 (5), p.441-454
• Main Authors: Pak, K. J., Ostrom, R. S., Matsui, M., Ehlert, F. J.
• Format: Article
• Language: English
• Subjects: Animals; Biomedical and Life Sciences; Biomedicine; Colforsin - pharmacology; Diabetes Mellitus, Experimental - complications; Diabetes Mellitus, Experimental - physiopathology; Disease Models, Animal; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Muscarinic Agonists - pharmacology; Muscle Contraction - drug effects; Neurosciences; Original; Original Article; Oxotremorine - analogs & derivatives; Oxotremorine - pharmacology; Pharmacology/Toxicology; Receptor, Muscarinic M2 - drug effects; Receptor, Muscarinic M2 - genetics; Receptor, Muscarinic M2 - metabolism; Receptor, Muscarinic M3 - drug effects; Receptor, Muscarinic M3 - metabolism; Streptozocin; Time Factors; Urinary Bladder - drug effects; Urinary Bladder - metabolism
• ISSN: 0028-1298; 1432-1912
• DOI: 10.1007/s00210-010-0509-6

We investigated the contractile roles of M 2 and M 3 muscarinic receptors in urinary bladder from streptozotocin-treated mice. Wild-type and M 2 muscarinic receptor knockout (M 2 KO) mice were given a single injection of vehicle or streptozotocin (125 mg kg −1 ) 2–24 weeks prior to bladder assays. The effect of forskolin on contractions elicited to the muscarinic agonist, oxotremorine-M, was measured in isolated urinary bladder (intact or denuded of urothelium). Denuded urinary bladder from vehicle-treated wild-type and M 2 KO mice exhibited similar contractile responses to oxotremorine-M, when contraction was normalized relative to that elicited by KCl (50 mM). Eight to 9 weeks after streptozotocin treatment, the EC 50 value of oxotremorine-M increased 3.1-fold in urinary bladder from the M 2 KO mouse ( N  = 5) compared to wild type ( N  = 6; P