title: Influence of streptozotocin diabetes on the alpha-1 adrenoceptor and associated G proteins in rat arteries.
abstract: Previous studies from this laboratory have demonstrated an enhancement in both the contractile and signaling response to stimulation of either alpha-1 adrenoceptors or guanine nucleotide binding proteins (G proteins) in arteries from male Wistar rats with 12 to 14 weeks of streptozotocin-induced diabetes. The purpose of the present investigation was to determine whether changes in arterial alpha-1 adrenoceptors or the G proteins coupled to them are associated with the enhanced responsiveness of the diabetic arteries. No difference in affinity was detected between control and diabetic aorta or caudal artery membranes in saturation binding of [3H]prazosin to alpha-1 adrenoceptors. However, the alpha-1 adrenoceptor number was significantly decreased in caudal artery but not aorta from diabetic rats. In competition binding experiments, a low-affinity and a high-affinity binding site for norepinephrine were detected in the absence of guanine nucleotides and NaCl in control arteries, whereas only the low-affinity site was detected in diabetic arteries, suggesting that coupling of the alpha-1 adrenoceptor to G proteins is impaired in diabetic aorta and caudal artery. The levels of immunoreactive Gi2,3alpha and Gq/11alpha were not different between control and diabetic aorta or caudal artery. Thus, not only do changes in the number and coupling of the alpha-1 adrenoceptor or level of G proteins not explain the enhanced contractile responses of diabetic arteries to norepinephrine, but also the changes in alpha-1 adrenoceptor binding would counteract the enhancement. Instead, an increase in the activity of the G proteins or phospholipase C-beta coupled to the alpha-1 adrenoceptor may be mediating the enhanced responsiveness elicited by alpha-1 adrenoceptor stimulation in diabetic arteries.
authors.affiliation: Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, B.C., Canada V6T 1Z3.
authors.forename: L P
authors.initials: LP
authors.lastname: Weber
authors.forename: K M
authors.initials: KM
authors.lastname: Macleod
mesh_terms: D000818:Animals; D001158:Arteries / Q000737:chemistry*; D001667:Binding, Competitive; D015153:Blotting, Western; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000032:analysis*; D006165:Guanylyl Imidodiphosphate / Q000494:pharmacology; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D018340:Receptors, Adrenergic, alpha-1 / Q000032:analysis*; D012965:Sodium Chloride / Q000494:pharmacology; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D013311:Streptozocin
chemical_list: D018340:Receptors, Adrenergic, alpha-1; D006165:Guanylyl Imidodiphosphate; D012965:Sodium Chloride; D013311:Streptozocin; D019204:GTP-Binding Proteins; D000254:Sodium-Potassium-Exchanging ATPase