Abstract
ABSTRACT: In adult animals, prolonged β-agonist expo-sore leads to down-regulation of β-adrenergic receptors and deseasitization. Prior evidence from our lab suggests that this may not occur in developing animals. To study this, we measured the response to graded epinephrine infusion [2.7, 5.5,13.6, 273 μmol(kg · min), (0.5, 1.0, 2.5, 5.0 μg/ (kg · mm)], myocardial β-agonist receptor density, and components of the receptor-cyclase system in newborn lambs before (n = 6) and after (n = 5) 3 d of continuous isopro-terenol administration (2 μg/kg/min). β-Adrenergic receptors were measured by radioligand binding. Epinephrine dose-response curves were analyzed for the threshold and slope for changes in mean blood pressure, systolic blood pressure, and heart rate versus plasma epinephrine levels. Despite 3 d of continuous isoproterenol infusion, we observed no desensitization of the hemodynamic response to epinephrine. There was a reduction in receptor density when expressed per membrane protein [1553 ± 19.5 (controls) versus 73.2 ± 3.8 fmol/mg protein (agonist exposed), p < 0.05], but no alteration in receptor density when expressed per g cardiac wet weight [258.8 ± 39.9 (controls) versus 406.8 ± 74.0 fmol/g wet weight (agonist exposed)). There was no alteration in agonist affinity or in adenylyl cydase activity after adjustment for membrane protein recovery. Prolonged β-agonist infusion in newborn lambs does not desensitize hemodynamk responses to infused epinephrine. We propose that receptor regulation in developing animals is fundamentally different than in adult animals.
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Stein, H., Oyama, K., Sapien, R. et al. Prolonged β-Agonist Infusion Does Not Induce Desensitization or Down-Regulation of β-Adrenergic Receptors in Newborn Sheep. Pediatr Res 31, 462–466 (1992). https://doi.org/10.1203/00006450-199205000-00009
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DOI: https://doi.org/10.1203/00006450-199205000-00009
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