Mammen G J, Handberg G M, Story M E, Pennefather J N
Department of Pharmacology, Monash University, Clayton, Victoria, Australia.
Eur J Pharmacol. 1987 Nov 10;143(2):229-35. doi: 10.1016/0014-2999(87)90537-1.
Responses of isolated preparations of longitudinal myometrium from the guinea-pig to fenoterol, salbutamol and isoprenaline were examined. Virgin adult guinea-pigs were treated (i) with oestradiol cypionate 20 micrograms/kg s.c. thrice weekly for two weeks; or (ii) as in (i) plus progesterone 3 mg/animal for the last four days. Other animals (diestrous; cycle days 6-10) were untreated. The order of potency of the agonists in inhibiting field stimulation-induced contractions of the preparations (isoprenaline greater than or equal to fenoterol greater than salbutamol) indicated interaction with beta 2-adrenoceptors. Oestrogen treatment enhanced the potency of isoprenaline 5-fold. Treatment with oestrogen plus progesterone enhanced the potency of all agonists 10- to 30-fold, and increased the mean maximum response to salbutamol. The mean pKD values for displacement by fenoterol of binding of (-)-[125I]cyanopindolol to membrane preparations from animals in both treatment groups were 5.57-5.92. These results raise the possibility that progesterone may enhance the coupling of beta 2-adrenoceptors to transduction mechanisms in the longitudinal myometrium from oestrogen-primed guinea-pigs.
研究了豚鼠离体纵行子宫肌层制剂对非诺特罗、沙丁胺醇和异丙肾上腺素的反应。成年未孕豚鼠接受如下处理：（i）皮下注射环戊丙酸雌二醇20微克/千克，每周3次，共2周；或（ii）按（i）处理，在最后4天加用黄体酮3毫克/只动物。其他动物（动情后期；周期第6 - 10天）未作处理。激动剂抑制制剂的场刺激诱导收缩的效价顺序（异丙肾上腺素≥非诺特罗＞沙丁胺醇）表明其与β2 - 肾上腺素受体相互作用。雌激素处理使异丙肾上腺素的效价增强5倍。雌激素加黄体酮处理使所有激动剂的效价增强10至30倍，并增加了对沙丁胺醇的平均最大反应。两个处理组动物的膜制剂中，非诺特罗置换（ - ） - [125I]氰基吲哚洛尔结合的平均pKD值为5.57 - 5.92。这些结果提示，黄体酮可能增强雌激素预处理的豚鼠纵行子宫肌层中β2 - 肾上腺素受体与转导机制的偶联。
