Protein kinase C and the sub-sensitivity and sub-reactivity of the diabetic rat prostate gland to noradrenaline

Concentration-response curves to noradrenaline (1 nM-100 μM) were obtained in prostates from 6-week streptozotocin diabetic, insulin-treated diabetic or control rats. Compared to the curve obtained in controls, those obtained in prostates from diabetic and insulin-treated diabetic rats were shifted rightward. The α₁-adrenoceptor antagonist, prazosin (100 nM), caused a rightward shift of the curves in prostates from all groups. In contrast, the uptake 1 inhibitor, nisoxetine (300 nM), only produced a leftward shift of the curves in prostates from control and insulin-treated diabetic rats. However, frequency-response curves obtained in prostates from both control and diabetic rats were shifted leftward by nisoxetine (300 nM). The concentration-response curve to the α₁-adrenoceptor agonist, methoxamine (10 nM-100 μM), obtained in prostates from diabetic rats was shifted rightward compared with controls. Calphostin C (500 nM), a protein kinase C inhibitor, caused a leftward shift of the curve in prostates from diabetic, but not control, rats. The protein kinase C inhibitor, bisindolylmaleimide I (500 nM), β-adrenoceptor antagonist, propranolol (500 nM) and muscarinic cholinoceptor antagonist, atropine (300 nM), had no effect on the noradrenaline concentration-response curves of prostates from control or diabetic rats. Our results suggest that diabetes reduces the sensitivity and reactivity of the prostate to noradrenaline-induced stimulation, and this reduction may be due to changes in protein kinase C activity.