Takayanagi I, Kawano K, Koike K
Department of Chemical Pharmacology, Toho University School of Pharmaceutical Sciences, Chiba, Japan.
Jpn J Pharmacol. 1990 Jul;53(3):359-66. doi: 10.1254/jjp.53.359.
To study the effect of aging on the beta-adrenergic receptor potency of isoprenaline, tracheas from 3-, 6-, 10-, 40- and 100-week-old guinea pigs were used as test tissues. The pD2 values (potency) of isoprenaline increased with age in tracheas treated with corticosterone, but decreased in untreated tracheas. The pA2 value of propranolol against isoprenaline estimated in the treated tracheas did not change with age. Specific binding of [3H]-dihydroalprenolol to the microsomal fractions from the tracheal muscles from 6-, 10- and 40-week-old guinea pigs was analyzed with Scatchard plots. The capacity of maximum binding sites of [3H]-dihydroalprenolol increased with increasing age, while its dissociation constant did not change. Age-related increase in the potency of isoprenaline in the tracheas treated with corticosterone is considered to be due to the increase in the total amount (density) of beta-adrenoceptors. However, the potency of the drug in untreated tracheas decreased with age. These results suggest that extraneuronal uptake plays an important role in the beta-adrenergic action of isoprenaline in older (40 and 100 weeks) guinea pigs.
为研究衰老对异丙肾上腺素β-肾上腺素能受体效能的影响,选用3周龄、6周龄、10周龄、40周龄和100周龄豚鼠的气管作为测试组织。在经皮质酮处理的气管中,异丙肾上腺素的pD2值(效能)随年龄增长而升高,但在未经处理的气管中则降低。在经处理的气管中,普萘洛尔对异丙肾上腺素的pA2值不随年龄变化。用Scatchard作图法分析了[3H]-二氢阿普洛尔与6周龄、10周龄和40周龄豚鼠气管肌肉微粒体部分的特异性结合。[3H]-二氢阿普洛尔最大结合位点的容量随年龄增长而增加,而其解离常数不变。皮质酮处理的气管中异丙肾上腺素效能的年龄相关性增加被认为是由于β-肾上腺素能受体总量(密度)的增加。然而,未经处理的气管中该药物的效能随年龄降低。这些结果表明,非神经元摄取在老年(40周龄和100周龄)豚鼠异丙肾上腺素的β-肾上腺素能作用中起重要作用。