Effects of ONO-2235, an aldose reductase inhibitor, on muscarinic receptors and contractile response of the urinary bladder in rats with streptozotocin-induced diabetes.
This study was conducted to evaluate effects of the aldose reductase inhibitor ONO-2235 on the contractile response to acetylcholine of the urinary bladder dome of streptozotocin-induced diabetes mellitus (DM) rats and simultaneously observe the changes in the function and number of muscarinic receptors and the sorbitol content of the bladder. The contractile response to acetylcholine increased 51% in the DM rat bladder dome compared to the normal rats; however, this was attenuated to a 10% increase by administration of 100 mg/kg ONO-2235 for 2 weeks. Treatment with ONO-2235 significantly decreased the specific [3H]quinuclidinyl benzilate binding in DM rats. However there was no significant dose-dependency among the ONO-2235-treated groups. The sorbitol levels of the sciatic nerve and the bladder were higher in the DM rats compared to the control rats; ONO-2235 decreased the level, although it did not completely reverse them to the control level. These results suggest that an aldose reductase inhibitor attenuates the increase of the muscarinic receptor number and normalizes the enhanced contractile response to acetylcholine caused by hyperglycemia and diuresis, probably through suppression of the polyol-pathway in the DM rat bladder dome.
Kanda
M
M
Department of Urology, Yamanashi Medical University, Japan.
Eto
K
K
Tanabe
N
N
Sugiyama
A
A
Hashimoto
K
K
Ueno
A
A
D000109:Acetylcholine / Q000494:pharmacology; D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors*; D000704:Analysis of Variance; D000818:Animals; D001667:Binding, Competitive; D001786:Blood Glucose / Q000032:analysis / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D004231:Diuresis; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D006943:Hyperglycemia / Q000503:physiopathology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D011976:Receptors, Muscarinic / Q000187:drug effects* / Q000378:metabolism; D012236:Rhodanine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D012584:Sciatic Nerve / Q000187:drug effects / Q000378:metabolism; D013012:Sorbitol / Q000378:metabolism; D053778:Thiazolidines; D014021:Tissue Preservation; D001743:Urinary Bladder / Q000187:drug effects* / Q000201:enzymology
D001786:Blood Glucose; D004791:Enzyme Inhibitors; D011976:Receptors, Muscarinic; D053778:Thiazolidines; C038131:epalrestat; D013012:Sorbitol; D012236:Rhodanine; D000449:Aldehyde Reductase; D000109:Acetylcholine