Chronic oxytocin pretreatment inhibits adenylyl cyclase activity in cultured rat myometrial cells.
Chronic oxytocin pretreatment inhibits adenylyl cyclase activity in cultured rat myometrial cells.
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长期催产素预处理可抑制培养的大鼠子宫肌细胞中的腺苷酸环化酶活性。
DOI：
10.1095/biolreprod59.5.1108
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发表时间：
1998
影响因子：
3.6
通讯作者：
Emala,CW
中科院分区：
文献类型：
--
作者：
Lindeman,KS;Hirshman,CA;Kuhl,JS;Levitsky,HI;Emala,CW
为了确定是否慢性催产素预处理抑制腺苷酸环化酶，我们比较了腺苷酸环化酶的活性，从培养的，永生化的大鼠子宫肌层细胞，未经处理或预处理24小时，催产素制备的膜。慢性催产素预处理（1 × 10− 5 M，持续24 h）使基础、三磷酸鸟苷（1 × 10− 5 M）、异丙肾上腺素（1 × 10− 4 M）、毛喉素（1 × 10− 5 M）、氯化锰（20 mM）或氟化钠（1 × 10− 2 M）刺激的腺苷酸环化酶活性降低27 ± 5%至39 ± 11%（n = 6，p< 0.05）。催产素预处理2 h（n = 5）未产生显著影响。为了了解催产素预处理降低腺苷酸环化酶途径活性的机制，我们比较了催产素或苯肾上腺素预处理对腺苷酸环化酶活性的影响，并确定了Giinhibition和蛋白激酶C（PKC）耗竭的影响。慢性（24小时）苯肾上腺素预处理（1 × 10− 4 M）的效果与催产素预处理（1 × 10− 5 M）的效果相似。用佛波醇12-肉豆蔻酸酯13-乙酸酯（1 × 10− 6 M，41 h）消耗PKC可防止催产素预处理（1 × 10− 5 M，24 h）减弱腺苷酸环化酶活性。百日咳毒素预处理（1.25 μg/ml，41 h）对鸡胚成纤维细胞增殖无明显抑制作用。这些发现表明，慢性催产素预处理脱敏腺苷酸环化酶途径的交叉调节机制，涉及激活Gq和PKC。
To determine whether chronic oxytocin pretreatment inhibits adenylyl cyclase, we compared adenylyl cyclase activity in membranes prepared from cultured, immortalized rat myometrial cells that were untreated or pretreated for 24 h with oxytocin. Chronic oxytocin pretreatment (1 × 10−5M for 24 h) attenuated basal, guanosine triphosphate (1 × 10−5M)-, isoproterenol (1 × 10−4M)-, forskolin (1 × 10−5M)-, MnCl2(20 mM)- or NaF (1 × 10−2M)-stimulated adenylyl cyclase activity by 27 ± 5% to 39 ± 11% (n = 6,p< 0.05). Oxytocin pretreatment for 2 h (n = 5) did not produce a significant effect. To understand the mechanism by which oxytocin pretreatment decreased activity of the adenylyl cyclase pathway, we compared effects of pretreatment with either oxytocin or phenylephrine on adenylyl cyclase activity and determined the effects of Giinhibition and protein kinase C (PKC) depletion. Chronic (24 h) phenylephrine pretreatment (1 × 10−4M) had effects similar to those of oxytocin pretreatment (1 × 10−5M). PKC depletion with phorbol 12-myristate 13-acetate (1 × 10−6M, 41 h) prevented attenuation of adenylyl cyclase activity by oxytocin pretreatment (1 × 10−5M for 24 h). Inhibition of Giby pertussis toxin pretreatment (1.25 μg/ml, 41 h) had no significant effect. These findings suggest that chronic oxytocin pretreatment desensitizes the adenylyl cyclase pathway by a cross-regulatory mechanism that involves activation of Gqand PKC.