Sun L S
Department of Anesthesiology and Pediatrics, Columbia University College of Physicians and Surgeons, New York, N.Y., USA.
Biol Neonate. 1999 Sep;76(3):181-92. doi: 10.1159/000014157.
beta-Adrenergic receptor (betaAR) desensitization is the decrease in response following sustained agonist stimulation by catecholamines. While developmental changes in betaAR response have been well documented in the mammalian heart, much less is known regarding the regulation of betaAR function in immature hearts. The purpose of the present study was to determine whether there are developmental differences in myocardial betaAR desensitization. We used an isolated heart preparation to examine the betaAR-mediated inotropic response before and after sustained exposure to 1 microM isoproterenol in adult and neonatal rabbits. We also assayed the adenylyl cyclase activity and performed radioligand-binding studies to determine betaAR characteristics in adult and neonatal ventricular tissues with and without exposure to isoproterenol. Both adult and neonatal rabbit hearts showed a concentration-dependent increase in systolic function, namely, isovolumic left ventricular developed pressure (LVDP) and maximal positive dP/dt of LVDP (dP/dt(max)) in response to isoproterenol. Adults, however, showed a significantly greater response than neonates. After sustained exposure to isoproterenol, the subsequent betaAR-mediated responses in LVDP and dP/dt(max) were significantly attenuated in adults, but much less so in neonates. The adenylyl cyclase activity in response to isoproterenol was significantly different between adult, but comparable in neonatal tissues both exposed or not to isoproterenol. The total betaAR density was higher in neonatal than in adult tissues without isoproterenol exposure, but there was no significant change in betaAR density in either group following isoproterenol exposure. In addition, isoproterenol exposure increased the amount of the inhibitory G protein in adult, but not neonatal tissues. Our results suggest that there were developmental differences in myocardial betaAR functional responses in betaAR desensitization.
β-肾上腺素能受体（βAR）脱敏是指在儿茶酚胺持续激动剂刺激后反应性降低。虽然哺乳动物心脏中βAR反应的发育变化已有充分记录，但关于未成熟心脏中βAR功能的调节知之甚少。本研究的目的是确定心肌βAR脱敏是否存在发育差异。我们使用离体心脏标本，检测成年和新生兔在持续暴露于1μM异丙肾上腺素前后βAR介导的变力反应。我们还测定了腺苷酸环化酶活性，并进行放射性配体结合研究，以确定成年和新生心室组织在暴露或未暴露于异丙肾上腺素情况下的βAR特性。成年和新生兔心脏对异丙肾上腺素的反应均表现为收缩功能呈浓度依赖性增加，即等容左心室发育压力（LVDP）和LVDP的最大正dP/dt（dP/dt(max)）增加。然而，成年兔的反应明显大于新生兔。持续暴露于异丙肾上腺素后，成年兔LVDP和dP/dt(max)随后的βAR介导反应明显减弱，但新生兔减弱程度小得多。成年组织中对异丙肾上腺素反应的腺苷酸环化酶活性有显著差异，但在新生组织中，无论是否暴露于异丙肾上腺素，该活性相当。在未暴露于异丙肾上腺素的情况下，新生组织中的总βAR密度高于成年组织，但两组在暴露于异丙肾上腺素后βAR密度均无显著变化。此外，异丙肾上腺素暴露增加了成年组织中抑制性G蛋白的量，但未增加新生组织中的量。我们的结果表明，在βAR脱敏过程中，心肌βAR功能反应存在发育差异。
