Changes in contractile responses of the urinary bladder to substance P in streptozotocin-induced diabetic rats.

1. Functional changes in the urinary bladder obtained from streptozotocin-induced diabetic rats were investigated by determining the responsiveness of bladder strips to capsaicin or substance P (SP). 2. Contractile responses of detrusor strips of the urinary bladder in response to capsaicin were almost abolished in both diabetic rats and capsaicin-pretreated rats. 3. Maximal contractions of diabetic detrusor strips induced by SP were significantly increased when compared to age-matched controls. 4. In contrast to the contractile responses to SP, the density of SP receptors was significantly decreased in diabetic rats. 5. The increased contractile responses to SP were markedly decreased by treatment with indomethacin, OKY-046 or quinacrine, but not with nordihydroguaiaretic acid. 6. Contractile responses of detrusor strips to prostaglandin F2 alpha and E2 were unchanged in the diabetic state. 7. These results suggest that the increased contractile responses of detrusor strips of the bladder to SP in the diabetic state are due to increased synthesis of prostaglandins and/or thromboxane A2 via the increased activity of phospholipase A2 on the smooth muscle of the diabetic bladder.