Ability of cyclohexenonic long-chain fatty alcohol to ameliorate diabetes-induced cystopathy in the rat.
We investigated the pharmacological effects of N-hexacosanol on diabetic rat detrusor. Eight-week-old male Sprague-Dawley rats were randomly divided into 4 groups: diabetic rats induced by 50 mg/kg intraperitoneally of streptozotocin treated with N-hexacosanol (0, 2 or 8 mg/kg, subcutaneously every day) and control rats. Bladder function was estimated by functional studies using carbachol and KCl. Contractile response curves to increasing concentrations of carbachol were constructed in the absence and presence of various concentrations of subtype-selective muscarinic antagonists, that is, atropine, pirenzepine, methoctramine and 4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP). The participation levels of muscarinic M(2) and M(3) receptor mRNAs in detrusor were investigated by real-time polymerase chain reaction. Treatment with N-hexacosanol did not alter diabetic status of the rats, but significantly improved the diabetes-induced hypercontractility of the rat bladder. Estimations of the pA(2) values for atropine, pirenzepine, methoctramine and 4-DAMP indicate that the carbachol-induced contractile response is mediated through the M(3) receptor subtype in all groups. Furthermore, N-hexacosanol ameliorated the diabetes-induced upregulation of muscarinic M(2) receptor mRNAs in streptozotocin-diabetic rat detrusor. Our data indicate that N-hexacosanol has therapeutic effects on hypercontractility in the diabetic bladder by ameliorating overexpression of muscarinic M(2) and M(3) receptor mRNAs without significant alternations of pharmacological profiles.
Kazuyama
Emi
E
Department of Pathophysiological and Therapeutic Science, Division of Molecular Pharmacology, Tottori University Faculty of Medicine, Yonago, Japan.
Saito
Motoaki
M
Okada
Shinichi
S
Satoh
Keisuke
K
D000818:Animals; D003512:Cyclohexanones / Q000627:therapeutic use*; D003921:Diabetes Mellitus, Experimental / Q000150:complications* / Q000188:drug therapy* / Q000503:physiopathology; D005233:Fatty Alcohols / Q000627:therapeutic use*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D001745:Urinary Bladder Diseases / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology
C420963:3-(15-hydroxypentadecyl)-2,4,4-trimethyl-2-cyclohexen-1-one; D003512:Cyclohexanones; D005233:Fatty Alcohols