Benediktsdóttir V E, Skúladóttir G V, Gudbjarnason S
Science Institute, University of Iceland, Reykjavík.
Eur J Pharmacol. 1995 May 26;289(3):419-27. doi: 10.1016/0922-4106(95)90150-7.
The purpose of this study was to examine the influence of ageing on the alterations in binding characteristics of adrenoceptors and membrane phospholipid fatty acids in rat heart following repeated administration of epinephrine. The maximal number of binding sites (Bmax) and dissociation constant (Kd) of [3H]prazosin and [3H]dihydroalprenolol binding to alpha 1- and beta-adrenoceptors, respectively, changed significantly during ageing. The downregulation of alpha 1- and beta-adrenoceptors after repeated epinephrine administration for one week, did not differ with age, but the response of the affinity (1/Kd) of both alpha 1- and beta-adrenoceptors to epinephrine treatment was age dependent. In 3-month-old rats the affinity of alpha 1-adrenoceptors was decreased after epinephrine treatment but the affinity of beta-adrenoceptors was unchanged. In 10- and 23-month-old rats the affinity of beta-adrenoceptors decreased after epinephrine treatment but the affinity of alpha 1-adrenoceptors did not change. During ageing the linoleic acid (18:2(n-6)) level decreased in phosphatidylcholine and the arachidonic acid (20:4(n-6)) level increased in phosphatidylcholine and phosphatidylethanolamine. After epinephrine administration the 18:2(n-6) level decreased and the docosahexaenoic acid (22:6(n-3)) level increased in phosphatidylcholine and phosphatidylethanolamine and those changes were not age dependent. The 20:4(n-6) level increased in phosphatidylcholine after epinephrine administration, but that increase was smaller in old than in young rats. The results show that both ageing and epinephrine administration simultaneously modify the fatty acid composition of membrane phospholipids and the binding properties of alpha 1- and beta-adrenoceptors in rat heart.
本研究旨在探讨衰老对大鼠心脏肾上腺素重复给药后肾上腺素能受体结合特性及膜磷脂脂肪酸变化的影响。[3H]哌唑嗪和[3H]二氢阿普洛尔分别与α1 -和β -肾上腺素能受体结合的最大结合位点数（Bmax）和解离常数（Kd）在衰老过程中发生了显著变化。肾上腺素重复给药一周后，α1 -和β -肾上腺素能受体的下调与年龄无关，但α1 -和β -肾上腺素能受体对肾上腺素治疗的亲和力（1/Kd）反应具有年龄依赖性。在3月龄大鼠中，肾上腺素治疗后α1 -肾上腺素能受体的亲和力降低，但β -肾上腺素能受体的亲和力未改变。在10月龄和23月龄大鼠中，肾上腺素治疗后β -肾上腺素能受体的亲和力降低，但α1 -肾上腺素能受体的亲和力未改变。在衰老过程中，磷脂酰胆碱中亚油酸（18:2(n - 6)）水平降低，磷脂酰胆碱和磷脂酰乙醇胺中花生四烯酸（20:4(n - 6)）水平升高。肾上腺素给药后，磷脂酰胆碱和磷脂酰乙醇胺中的18:2(n - 6)水平降低，二十二碳六烯酸（22:6(n - 3)）水平升高，且这些变化与年龄无关。肾上腺素给药后，磷脂酰胆碱中的20:4(n - 6)水平升高，但老年大鼠的升高幅度小于年轻大鼠。结果表明，衰老和肾上腺素给药同时改变了大鼠心脏膜磷脂的脂肪酸组成以及α1 -和β -肾上腺素能受体的结合特性。
