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衰老大鼠肝脏中高亲和力α1 - 肾上腺素能受体减少:不同温度下评估的意义

Reduced high-affinity alpha 1-adrenoceptors in liver of senescent rats: implications of assessment at various temperatures.

作者信息

Borst S E, Scarpace P J

机构信息

Geriatric Research, Education and Clinical Center, DVA Medical Center, Gainesville, FL 32602.

出版信息

Br J Pharmacol. 1990 Nov;101(3):650-4. doi: 10.1111/j.1476-5381.1990.tb14135.x.

Abstract
  1. We investigated the changes occurring as a result of aging in alpha 1-adrenoceptors in the livers of Fisher 344 females rats. For comparison, we also measured beta-adrenoceptors in this tissue. Three age groups were studied, including young adults (aged 6 months), mature adults (aged 16 months) and senescent animals (aged 25 months). 2. The density of alpha 1-receptors was measured by use of [3H]-prazosin and was found to be reduced 39% (P less than 0.01) at 25 months compared with 6 months. The percentage of alpha 1-receptors displaying high affinity for adrenaline was also reduced from 85.6% at 6 months to 51.6% at 25 months (P less than 0.02). 3. In contrast, the density of beta-receptors, which was measured with [125I]-iodocyanopindolol, was increased 104% between 6 months and 25 months. The affinity of both alpha 1- and beta-adrenoceptors for antagonists was unchanged with age. 4. We found that receptor affinity for agonists may be measured accurately in binding studies conducted at 4 degrees C or 25 degrees C, but that the apparent affinity for agonist was artifactually reduced in studies conducted at 37 degrees C. This effect is poorly reversible, in that reduced agonist-affinity is also observed in tissue which has been incubated at 37 degrees C and then cooled to 4 degrees C before performing the binding studies. 5. It is concluded that liver alpha 1-adrenoceptor function is reduced and beta-adrenoceptor function increased in senescence.
摘要
  1. 我们研究了衰老对费希尔344雌性大鼠肝脏中α1 - 肾上腺素能受体的影响。为作比较,我们还测量了该组织中的β - 肾上腺素能受体。研究了三个年龄组,包括青年成年鼠(6个月龄)、成年成熟鼠(16个月龄)和衰老动物(25个月龄)。

  2. 使用[3H] - 哌唑嗪测量α1受体的密度,发现与6个月龄相比,25个月龄时密度降低了39%(P < 0.01)。对肾上腺素显示高亲和力的α1受体百分比也从6个月龄时的85.6%降至25个月龄时的51.6%(P < 0.02)。

  3. 相比之下,用[125I] - 碘氰吲哚洛尔测量的β受体密度在6个月至25个月之间增加了104%。α1和β肾上腺素能受体对拮抗剂的亲和力不随年龄变化。

  4. 我们发现,在4℃或25℃进行的结合研究中,可以准确测量受体对激动剂的亲和力,但在37℃进行的研究中,激动剂的表观亲和力会人为降低。这种效应很难逆转,因为在37℃孵育后再冷却至4℃进行结合研究的组织中也观察到激动剂亲和力降低。

  5. 结论是,衰老过程中肝脏α1 - 肾上腺素能受体功能降低,β - 肾上腺素能受体功能增加。

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