PT  - JOURNAL ARTICLE
AU  - K. J. Pak
AU  - R. S. Ostrom
AU  - M. Matsui
AU  - F. J. Ehlert
TI  - The M<sub>2</sub>-Muscarinic Receptor Inhibits the Development of Streptozotocin-Induced Neuropathy in Mouse Urinary Bladder
AID  - 10.1124/jpet.110.169995
DP  - 2010 Oct 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 239--248
VI  - 335
IP  - 1
4099  - http://jpet.aspetjournals.org/content/335/1/239.short
4100  - http://jpet.aspetjournals.org/content/335/1/239.full
SO  - J Pharmacol Exp Ther2010 Oct 01; 335
AB  - We investigate the role of M2-muscarinic receptors in maintaining neurogenic bladder contraction during hyperglycemia. Mice were injected with a single dose of streptozotocin (125 mg/kg), and neurogenic contraction of urinary bladder from wild type and M2-muscarinic receptor knockout (M2 KO) mice was measured at 8 to 24 weeks after treatment. In wild-type bladder lacking urothelium, the summation of the cholinergic (64%) and purinergic (56%) components of the electrical-field-stimulated response exceeded 100%, indicating a reserve capacity. Although the cholinergic component was slightly less in the M2 KO mouse, the total electrical-field-stimulated contraction was the same as wild type. The cholinergic and purinergic components of contraction in wild-type bladder were minimally affected by streptozotocin treatment. In M2 KO bladder, streptozotocin treatment reduced both the cholinergic (after 8–9 and 20–24 weeks) and purinergic (after 20–24 weeks only) components. The loss of function was approximately 50 to 70%. Similar results were observed in bladder with intact urothelium. M2 KO bladder was more sensitive to the relaxant effect of isoproterenol compared with wild type, and this difference significantly increased at the early and late time points after streptozotocin treatment. In the presence of urothelium, however, this difference in isoproterenol sensitivity was smaller with streptozotocin treatment, but this trend reversed over time. Our results show that M2 receptors oppose urinary bladder distension in wild-type bladder and inhibit streptozotocin-induced neuropathy.