The M2 muscarinic receptor inhibits the development of streptozotocin-induced neuropathy in mouse urinary bladder.
The Journal of pharmacology and experimental therapeutics 2010 Jul 12; In press
Pak K, Ostrom R RS, Matsui M, Ehlert F FJ
1 University of California - Irvine;
We investigate the role of the M(2) muscarinic receptor 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 M(2) muscarinic receptor knockout (M(2) KO) mice was measured 8-24 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 a little less in the M(2) 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 M(2) KO bladder, streptozotocin treatment reduced both the cholinergic (after 8-9 weeks and 20-24 weeks) and purinergic (after 20-24 weeks only) components. The loss of function was about 50-70%. Similar results were observed in bladder with intact urothelium. M(2) KO bladder was more sensitive to the relaxant effect of isoproterenol compared to 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 M(2) receptors oppose urinary bladder distension in wild type bladder and inhibit STZ-induced neuropathy.
Keywords: diabetes diabetic neuropathy