The Role of Rac1 on Carbachol-induced Contractile Activity in Detrusor Smooth Muscle from Streptozotocin-induced Diabetic Rats.
This study was designed to determine the role of the small GTPase Rac1 on carbachol-induced contractile activity in detrusor smooth muscle using small inhibitor NSC 23766 in diabetic rats. Rac1 expression in bladder tissue was also evaluated. In the streptozotocin (STZ)-induced diabetic rat model, three study groups were composed of control, diabetic and insulin-treated diabetic subjects. The detrusor muscle strips were suspended in organ baths at the end of 8-12 weeks after STZ injection. Carbachol (CCh) (10(-9) -10(-4) M) concentration-response curves were obtained both in the absence and in the presence of Rac1 inhibitor NSC 23766 (0.1, 1 and 10 μM). Diabetes-related histopathological changes and Rac1 expressions were assessed by haematoxylin and eosin staining and immunohistochemical staining, respectively. CCh caused dose-dependent contractile responses in all the study groups. Rac1 inhibitor NSC 23766 inhibited CCh-induced contractile responses in all groups, but this inhibition seen in both diabetes groups was greater than in the control group. Histological examination revealed an increased bladder wall thickness both in the diabetes and in the insulin-treated diabetes groups compared to the control group. In immunohistochemical staining, expression of Rac1 was observed to be increased in all layers of bladder in both diabetic groups compared to the control group. In the diabetic bladders, increased expression of Rac1 and considerable inhibition of CCh-induced responses in the presence of NSC 23766 compared to those of the control group may indicate a specific role of Rac1 in diabetes-related bladder dysfunction, especially associated with cholinergic mediated detrusor overactivity.
Department of Pharmacology, School of Medicine, Dokuz Eylul University, Izmir, Turkey.
Atiye Sinem
AS
Evcim
Serap Cilaker
SC
Micili
Meral
M
Karaman
Guven
G
Erbil
Ensari
E
Guneli
Sedef
S
Gidener
Mukaddes
M
Gumustekin
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D002217:Carbachol / Q000494:pharmacology*; D048909:Diabetes Complications / Q000503:physiopathology; D003921:Diabetes Mellitus, Experimental / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D018721:Muscarinic Agonists / Q000494:pharmacology*; D009119:Muscle Contraction / Q000187:drug effects*; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D001743:Urinary Bladder / Q000187:drug effects* / Q000473:pathology; D001745:Urinary Bladder Diseases / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology*; D020830:rac1 GTP-Binding Protein / Q000502:physiology*
D001786:Blood Glucose; D018721:Muscarinic Agonists; D002217:Carbachol; C499134:Rac1 protein, rat; D020830:rac1 GTP-Binding Protein