Satoh M, Takayanagi I
Department of Chemical Pharmacology, Toho University School of Pharmaceutical Sciences, Chiba, Japan.
Jpn J Pharmacol. 1992 Apr;58(4):383-9. doi: 10.1254/jjp.58.383.
Single cells were prepared from guinea pig tracheal smooth muscle and used in an experiment on the contraction mechanisms for norepinephrine and a study on the change of alpha 2-adrenoceptors with age. Specific bindings of [3H]p-aminoclonidine to the single cells from the tracheal smooth muscles of 6- and 40-week-old guinea pigs were saturable and analyzed by Scatchard plot. The maximum number of [3H]p-aminoclonidine binding sites was larger in the preparation from 40-week-old guinea pigs than that from 6-week-old animals, while its dissociation constant did not change with age. The amount of prostaglandin F2 alpha released from the single cells was increased by norepinephrine, not affected by phenylephrine, and reduced by an alpha 2-antagonist such as yohimbine. The amount released by norepinephrine was significantly larger in the preparation from 6-week-old guinea pigs than that from 40-week-old animals. These results suggest that the age-related decrease in the potency of norepinephrine is due to reduction in the amount of excitable prostaglandin F2 alpha released by the drug, but not to a change in the total amount of alpha 2-adrenoceptors or the dissociation constant of the drug with respect to these adrenoceptors. Furthermore, alpha 2-adrenoceptors in the tracheal smooth muscle cell play an important role in the release of prostaglandin F2 alpha and the production of contractile responses of these muscles.
从豚鼠气管平滑肌制备单细胞,并用于去甲肾上腺素收缩机制的实验以及α2 -肾上腺素能受体随年龄变化的研究。用[3H] -对氨基可乐定与6周龄和40周龄豚鼠气管平滑肌单细胞进行特异性结合,其结合呈饱和性,并通过Scatchard作图进行分析。40周龄豚鼠制备物中[3H] -对氨基可乐定结合位点的最大数量比6周龄动物的制备物中的大,而其解离常数不随年龄变化。单细胞释放的前列腺素F2α量可被去甲肾上腺素增加,不受苯肾上腺素影响,并被育亨宾等α2拮抗剂减少。6周龄豚鼠制备物中去甲肾上腺素释放的量比40周龄动物的显著更大。这些结果表明,去甲肾上腺素效力的年龄相关下降是由于该药物释放的可兴奋前列腺素F2α量减少,而非α2 -肾上腺素能受体总量的变化或该药物相对于这些肾上腺素能受体的解离常数的变化。此外,气管平滑肌细胞中的α2 -肾上腺素能受体在前列腺素F2α的释放以及这些肌肉收缩反应的产生中起重要作用。