ENHANCEMENT OF MUSCARINIC RECEPTOR-COUPLED PHOSPHATIDYL-INOSITOL HYDROLYSIS IN DIABETIC BLADDER

We previously have shown an increase in muscarinic receptor density in streptozotocin (STZ)-induced diabetic and sucrose-fed diuretic rat de trusor that correlates with an increase in the contractile response to muscarinic agonist (J Pharmacol Exp Ther 248:81, 1989; Diabetes 40:26 5, 1991). To investigate the signal transduction pathway involved in t his altered functional response, we examined muscarinic receptor-coupl ed phosphatidylinositol metabolism in STZ-diabetic, sucrose-fed diuret ic and age-matched control rat bladders. [H-3]myo-inositol uptake was similar in all groups, but incorporation of myo-inositol into phosphat idylinositol (PI) was significantly increased in the diabetic bladder compared to the sucrose-fed and control rat bladders. Carbachol-induce d increase in inositol phosphate (IPs) production was higher in the di abetic bladder than in bladders from control and sucrose-fed animals a lthough the EC(50) values were similar for all groups. Enhanced inosit ol phosphate production after muscarinic agonist stimulation may be du e not only to the upregulation of muscarinic receptors but also to the increased incorporation of myo-inositol into PI in the STZ-induced di abetic bladder.