Feng Z P, Dryden W F, Gordon T
Department of Pharmacology, University of Alberta, Edmonton, Canada.
Can J Physiol Pharmacol. 1989 Aug;67(8):883-9. doi: 10.1139/y89-138.
It is uncertain how changes in the beta-adrenoceptor population influence the contractility of developing heart. To resolve this we have examined postnatal developmental changes in the adrenergic responsiveness of the rabbit heart. The inotropic effect of isoproterenol on isolated left ventricular papillary muscles from rabbits aged 3, 21, and 90 days was compared with the relative number of beta-adrenoceptors at each age measured using [3H]dihydroalprenolol ([3H]DHA) as the specific ligand. The maximum tension developed in response to isoproterenol increases from 37 +/- 7 to 175 +/- 33% above control twitch tension between 3 and 21 days of age; this is followed by a decrease to 68 +/- 12% in the young adult. During this period of development, there is a decline in EC50 towards increased sensitivity. These differences are partially accounted for by an increase in the numbers of specific [3H]DHA binding sites from 17.3 +/- 2.3 to 56.6 +/- 9.9 fmol/mg wet tissue weight from 3 to 21 days, and a subsequent decrease to 32 +/- 4.5 fmol/mg tissue in the young adult. The proportionally larger increase in contractility compared with the number of beta-adrenoceptor binding sites during the first 3 weeks of life is discussed in terms of the developmental changes in the efficacy of coupling between receptor occupancy and contraction.
β-肾上腺素能受体数量的变化如何影响发育中心脏的收缩性尚不确定。为了解决这个问题，我们研究了家兔心脏肾上腺素能反应性的出生后发育变化。将异丙肾上腺素对3日龄、21日龄和90日龄家兔离体左心室乳头肌的变力作用，与使用[3H]二氢阿普洛尔（[3H]DHA）作为特异性配体测定的各年龄阶段β-肾上腺素能受体的相对数量进行了比较。异丙肾上腺素引起的最大张力在3日龄至21日龄之间从对照抽搐张力以上的37±7%增加到175±33%；在年轻成年期则降至68±12%。在这个发育阶段，EC50下降，敏感性增加。这些差异部分是由于特异性[3H]DHA结合位点的数量从3日龄时的17.3±2.3 fmol/mg湿组织重量增加到21日龄时的56.6±9.9 fmol/mg湿组织重量，随后在年轻成年期降至32±4.5 fmol/mg组织。根据受体占据与收缩之间偶联效率的发育变化，讨论了出生后前三周收缩性与β-肾上腺素能受体结合位点数量相比成比例更大增加的情况。
