Lyon M E, Lefebvre C A, Davis D J
Department of Pediatrics and Obstetrics/Gynecology, University of Ottawa, Ontario, Canada.
Thorax. 1994 Jul;49(7):664-9. doi: 10.1136/thx.49.7.664.
Suitable models for the study of lung development are needed. The suitability of the guinea pig for studying the role of the beta adrenergic response cascade in fetal lung development has been evaluated.
Radioligand binding assays with iodine-125 labelled iodopindolol were performed to identify and characterise the beta adrenergic receptors. To demonstrate that these receptors were functional, isoprenaline and forskolin stimulated generation of cyclic AMP (cAMP) in the lung tissue was quantitated by radioimmunoassay.
The concentration of beta receptors increased with gestational age from 23 fmol/mg at 35 days to 140 fmol/mg at 64 days. Competition binding studies were consistent with a predominance of beta 2 receptors. The ability of isoprenaline to stimulate cAMP generation was greater during the saccular phase than during the canalicular phase of lung development. Incorporation of tritium labelled choline into phosphatidylcholine increased significantly between the canalicular and saccular phases.
The beta adrenergic response cascade in fetal guinea pig lung exhibits similar characteristics to those previously described in fetal human lung and is therefore a good model in which to study the effects of beta agonists on fetal lung development.
需要适合研究肺发育的模型。已评估豚鼠在研究β肾上腺素能反应级联在胎儿肺发育中的作用方面的适用性。
采用125碘标记的吲哚洛尔进行放射性配体结合试验,以鉴定和表征β肾上腺素能受体。为证明这些受体具有功能,通过放射免疫分析法对异丙肾上腺素和福斯高林刺激肺组织中环状AMP(cAMP)生成的情况进行定量。
β受体浓度随胎龄增加,从35天时的23 fmol/mg增至64天时的140 fmol/mg。竞争结合研究表明β2受体占优势。在肺发育的囊状期,异丙肾上腺素刺激cAMP生成的能力比小管期更强。从小管期到囊状期,氚标记胆碱掺入磷脂酰胆碱的量显著增加。
胎儿豚鼠肺中的β肾上腺素能反应级联表现出与先前在胎儿人肺中描述的相似特征,因此是研究β激动剂对胎儿肺发育影响的良好模型。