Chen F C, Yamamura H I, Roeske W R
J Pharmacol Exp Ther. 1982 Jul;222(1):7-13.
We have demonstrated previously a postnatal peak for the beta adrenergic receptor in the heart and detected the appearance of a beta adrenergic receptor before an (-)-isoproterenol inducible increase in heart rate. The present study examined 1) agonist displaceable [3H] dihydroalprenolol (DHA) binding in the neonatal and adult mouse heart and 2) adenylate cyclase in fetal, neonatal and adult mouse heart. 3[H]DHA binding displaceable by (-)-isoproterenol gave a similar Ki from 1 day neonate through adult. Similar to the result found for antagonist displacement binding, there was a dramatic increase in the agonist displaceable [3H] DHA binding postnatally. The maximum was achieved in 2 weeks and then gradually declined to adult level. Cyclase activity (basal, (-)-isoproterenol- and NaF- stimulated) paralleled beta adrenergic receptor increases before birth. However, no early postnatal peak was present. In the 13 day fetal mouse heart, there is no (-)-isoproterenol increase in heart rate, but beta adrenergic receptor (13 +/- 4% of adult) and (-)-isoproterenol-stimulated adenylate cyclase activity (15 +/- 5% of adult) are present. It is concluded that 1) no significant difference exists between the agonist and antagonist displaceable [3H] DHA binding during development, 2) adenylate cyclase activity increases significantly during the last third of pregnancy in parallel with the beta adrenergic receptor, 3) both the beta adrenergic receptor and adenylate cyclase activity can be detected before the heart rate responses and 4) total adenylate cyclase activity does not increase in parallel with the early postnatal beta adrenergic receptor peak.
我们之前已经证明,心脏中的β肾上腺素能受体在出生后会出现一个峰值,并且在(-)-异丙肾上腺素诱导心率增加之前就检测到了β肾上腺素能受体的出现。本研究检测了:1)新生和成年小鼠心脏中激动剂可置换的[3H]二氢心得舒(DHA)结合;2)胎儿、新生和成年小鼠心脏中的腺苷酸环化酶。(-)-异丙肾上腺素可置换的3[H]DHA结合,从出生1天的新生儿到成年小鼠,其解离常数(Ki)相似。与拮抗剂置换结合的结果相似,激动剂可置换的[3H]DHA结合在出生后显著增加。在2周时达到最大值,然后逐渐下降至成年水平。环化酶活性(基础、(-)-异丙肾上腺素和氟化钠刺激的)在出生前与β肾上腺素能受体的增加平行。然而,出生后早期没有峰值出现。在13天的胎儿小鼠心脏中,(-)-异丙肾上腺素不会使心率增加,但存在β肾上腺素能受体(为成年小鼠的13±4%)和(-)-异丙肾上腺素刺激的腺苷酸环化酶活性(为成年小鼠的15±5%)。研究得出以下结论:1)在发育过程中,激动剂和拮抗剂可置换的[3H]DHA结合之间不存在显著差异;2)腺苷酸环化酶活性在妊娠最后三分之一期间与β肾上腺素能受体平行显著增加;3)在心率反应之前就能检测到β肾上腺素能受体和腺苷酸环化酶活性;4)总腺苷酸环化酶活性与出生后早期β肾上腺素能受体峰值不平行增加。