title: Possibility of inhibition of calcium-activated chloride channel rescuing erectile failures in diabetes.
abstract: Although calcium-activated chloride channel (CaCC) blockers, niflumic acid (NFA) and anthracene-9-carboxylic acid (A9C), have been shown as potential erectogenic agents in healthy corpus cavernosum (CC) tissues, the pharmacological characteristics of CaCC blockers in diabetic state are relatively unknown. This study compares the direct muscle relaxant property of NFA and A9C with their influence on contraction and nitrergic relaxation as elicited by electrical field stimulation in normal and 16-week-old diabetic rabbit CC (n=8). Mean blood glucose level in alloxan-treated rabbits was elevated threefold (21.9±0.5 mmol  l(-1) vs 7.1±0.2 mmol l(-1) in untreated rabbits; P<0.05). There was no significant alteration in the efficacies of NFA and A9C in eliciting a concentration-dependent relaxation of noradrenaline-induced cavernosum tone and in inhibiting neurogenic contraction of CC from diabetic rabbits. The capability of NFA (100 μM) and A9C (1 mM) in augmenting nitrergic transmission was also not adversely affected by diabetes. However, in CC from diabetic rabbits, A9C markedly increased nitrergic relaxation response to 1-10 Hz by 10.6-36.6% (vs -5.1-0.8% in nondiabetic control). CaCC sensitivity to A9C appears to be enhanced in diabetic CC tissue. Inhibiting the CaCC activity in diabetes-related ED may tip the balance between proerectile/relaxant and antierectile/contractile mechanisms in favor of cavernosum relaxation.
authors: Department of Obstetrics and Gynaecology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
authors: L-C
authors: LC
authors: Lau
authors: Department of Obstetrics and Gynaecology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
authors: P G
authors: PG
authors: Adaikan
mesh_terms: D000818:Animals; D000873:Anthracenes / Q000494:pharmacology / Q000627:therapeutic use; D018118:Chloride Channels / Q000037:antagonists & inhibitors*; D048909:Diabetes Complications / Q000188:drug therapy*; D003921:Diabetes Mellitus, Experimental / Q000150:complications*; D004558:Electric Stimulation; D007172:Erectile Dysfunction / Q000188:drug therapy* / Q000209:etiology*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000503:physiopathology; D009544:Niflumic Acid / Q000494:pharmacology / Q000627:therapeutic use; D010410:Penile Erection / Q000187:drug effects; D010413:Penis / Q000737:chemistry / Q000503:physiopathology; D011817:Rabbits
chemical_list: D000873:Anthracenes; D018118:Chloride Channels; D009544:Niflumic Acid; C010030:9-anthroic acid