title: Protein kinase C and the sub-sensitivity and sub-reactivity of the diabetic rat prostate gland to noradrenaline.
abstract: Concentration-response curves to noradrenaline (1 nM-100 microM) 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 alpha1-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 alpha1-adrenoceptor agonist, methoxamine (10 nM-100 microM), 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), beta-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.
authors.affiliation: Department of Pharmacology, P.O. Box 13E, Monash University, Victoria 3800, Australia.
authors.forename: Sharmaine
authors.initials: S
authors.lastname: Ramasamy
authors.forename: Wayne C
authors.initials: WC
authors.lastname: Hodgson
authors.forename: Sabatino
authors.initials: S
authors.lastname: Ventura
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005473:Fluoxetine / Q000031:analogs & derivatives* / Q000494:pharmacology; D007150:Immunohistochemistry; D007211:Indoles / Q000494:pharmacology; D008297:Male; D008301:Maleimides / Q000494:pharmacology; D008729:Methoxamine / Q000494:pharmacology; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009281:Naphthalenes / Q000494:pharmacology; D009638:Norepinephrine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D011224:Prazosin / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D011467:Prostate / Q000187:drug effects* / Q000378:metabolism; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D004791:Enzyme Inhibitors; D007211:Indoles; D008301:Maleimides; D018727:Muscarinic Antagonists; D009281:Naphthalenes; D005473:Fluoxetine; C011386:nisoxetine; D001285:Atropine; D011433:Propranolol; D011493:Protein Kinase C; D008729:Methoxamine; C058819:calphostin C; C070515:bisindolylmaleimide I; D009638:Norepinephrine; D011224:Prazosin