PT - JOURNAL ARTICLE AU - Lynn P. Weber AU - Kathleen M. Macleod TI - Influence of Streptozotocin Diabetes on the<em>Alpha</em>-1 Adrenoceptor and Associated G Proteins in Rat Arteries DP - 1997 Dec 01 TA - Journal of Pharmacology and Experimental Therapeutics PG - 1469--1478 VI - 283 IP - 3 4099 - http://jpet.aspetjournals.org/content/283/3/1469.short 4100 - http://jpet.aspetjournals.org/content/283/3/1469.full SO - J Pharmacol Exp Ther1997 Dec 01; 283 AB - Previous studies from this laboratory have demonstrated an enhancement in both the contractile and signaling response to stimulation of eitheralpha-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 arterialalpha-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 Gi2,3α and Gq/11α were not different between control and diabetic aorta or caudal artery. Thus, not only do changes in the number and coupling of thealpha-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-β coupled to the alpha-1 adrenoceptor may be mediating the enhanced responsiveness elicited by alpha-1 adrenoceptor stimulation in diabetic arteries. The American Society for Pharmacology and Experimental Therapeutics