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[3H]萝芙辛与妊娠豚鼠子宫肌层α2-肾上腺素能受体的结合

[3H]rauwolscine binding to myometrial alpha 2-adrenoceptors in pregnant guinea pig.

作者信息

Arkinstall S J, Jones C T

机构信息

Laboratory of Developmental Physiology, Nuffield Institute for Medical Research, University of Oxford, United Kingdom.

出版信息

Am J Physiol. 1988 Sep;255(3 Pt 1):E272-9. doi: 10.1152/ajpendo.1988.255.3.E272.

DOI:10.1152/ajpendo.1988.255.3.E272
PMID:2844098
Abstract

Uterine sympathetic nerves can exert an excitatory influence in late pregnancy and during parturition. Neuronal norepinephrine release is increased at these times and a diminished alpha 2-adrenoceptor-mediated prejunctional inhibition could account for this. To assess whether an altered receptor population may contribute, [3H]rauwolscine was used to measure alpha 2-adrenoceptors in myometrial membranes at time intervals throughout pregnancy. High affinity [3H]rauwolscine binding [Kd = 11.4 +/- 1.5 nM (n = 42)] yielded linear Scatchard plots that in nonpregnant myometrium indicated a maximum binding density (Bmax) of 217 +/- 42.4 fmol/mg protein. alpha 2-Adrenoceptor density was increased twofold at midpregnancy (31 days) and thereafter fell sharply by up to 90% toward term (67 +/- 2 days). When uterine growth is accounted for and data are expressed in terms of total myometrial population (uncorrected for plasma membrane recovery), alpha 2-adrenoceptor number was eightfold (midpregnancy) and fourfold (term) greater than the nonpregnant value of 804 +/- 322.4 fmol/uterus. alpha 2-Adrenoceptors were also found to bind dopamine with high affinity [Ki = 3.66 +/- 0.45 microM (n = 3)]. These observations could indicate a pregnancy-related change in uterine sympathetic autoinhibitory capacity and, since alpha 2-adrenoceptors appear also to be located postjunctionally, explain in part reports of altered myometrial responsiveness to norepinephrine infusion and also the uterotonic actions of dopamine.

摘要

子宫交感神经在妊娠晚期及分娩过程中可发挥兴奋作用。在这些时期,神经元去甲肾上腺素释放增加,α2-肾上腺素能受体介导的突触前抑制减弱可能是其原因。为了评估受体数量的改变是否起作用,在整个孕期的不同时间间隔,使用[3H]萝芙辛来测量子宫肌层膜中的α2-肾上腺素能受体。高亲和力的[3H]萝芙辛结合[解离常数(Kd)= 11.4±1.5 nM(n = 42)]产生线性Scatchard图,在未孕子宫肌层中显示最大结合密度(Bmax)为217±42.4 fmol/mg蛋白质。在妊娠中期(31天),α2-肾上腺素能受体密度增加两倍,此后在足月时(67±2天)急剧下降高达90%。当考虑子宫生长并以子宫肌层总体数量表示数据(未校正质膜恢复)时,α2-肾上腺素能受体数量在妊娠中期为未孕时804±322.4 fmol/子宫值的八倍,在足月时为四倍。还发现α2-肾上腺素能受体以高亲和力结合多巴胺[抑制常数(Ki)= 3.66±0.45 μM(n = 3)]。这些观察结果可能表明子宫交感神经自身抑制能力存在与妊娠相关的变化,并且由于α2-肾上腺素能受体似乎也位于突触后,这部分解释了子宫肌层对去甲肾上腺素输注反应性改变的报道以及多巴胺的子宫收缩作用。

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